Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism

Morphogens act in developing tissues to control the spatial arrangement of cellular differentiation. The activity of a morphogen has generally been viewed as a concentration-dependent response to a diffusible signal, but the duration of morphogen signalling can also affect cellular responses. One such example is the morphogen sonic hedgehog (SHH). In the vertebrate central nervous system and limbs, the pattern of cellular differentiation is controlled by both the amount and the time of SHH exposure. How these two parameters are interpreted at a cellular level has been unclear. Here we provide evidence that changing the concentration or duration of SHH has an equivalent effect on intracellular signalling. Chick neural cells convert different concentrations of SHH into time-limited periods of signal transduction, such that signal duration is proportional to SHH concentration. This depends on the gradual desensitization of cells to ongoing SHH exposure, mediated by the SHH-dependent upregulation of patched 1 (PTC1), a ligand-binding inhibitor of SHH signalling. Thus, in addition to its role in shaping the SHH gradient, PTC1 participates cell autonomously in gradient sensing. Together, the data reveal a novel strategy for morphogen interpretation, in which the temporal adaptation of cells to a morphogen integrates the concentration and duration of a signal to control differential gene expression.     

Measurement Preconditions Systemic Action: The Case of Integral Low-Carbon Country and Sustainable Development Indicators

Sustainable development (SD) belongs to objectives of social responsibility (SR), including the ‘integral low-carbon societies’, as an objective and effort. This article presents the concept of low-carbon Slovenia and indicators of sustainable development (SDI) in Croatia and Slovenia that help in measurement efforts. Indicators reflect the national sets of SDI, developed recently; one focuses on EU and comparison with other regions in the world. Key challenges include (1) making a low-carbon country reality, (2) comparability and aggregation variability of SDI determined by SD policies; (3) SR, as a contribution to, and framework of, sustainability, as a requisitely holistic approach to current problems, based on ethics of interdependence of humans and other nature.     

CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.     

A survey and assessment of the rare vascular plants of the Idaho National Engineering Laboratory site

A two-year study of the rare vascular plants of the Idaho National Engineering Laboratory generated new data on the abundance, distribution, and habitat features of eight taxa presently under review at either the federal or state level, or recently proposed for such review. Astragalus ceramicus Sheld. var. apus Barneby is common on the INEL and adjacent areas and will be recommended for removal from further consideration at the federal level and placed on Idaho's Federal Watch List. Coryphanta missouriensis (Sweet) Britt. & Rose is common throughout east central Idaho, but will be recommended for retainment on the State Watch List. Gymnosteris nudicaulis (H. & A.) Greene and Oxytheca dendroidea Nutt. are also recommended for retention on the State Watch List. Four taxa not previously known to occur in Idaho or not known from the southeastern part of the state ( Astragalus gilviflorus Sheld., Astragalus kentrophyta Gray var. jessiae (Peck) Barneby, Gilia polycladon Torr., and Lesquerella kingii S. Wats. var. cobrensis Roll. & Shaw) were encountered and evaluated with reference to current or potential threats, and are recommended for placement on Idaho's State Watch List.         

Genome evolution in yeasts

Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss.     

Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification

Idiopathic infantile arterial calcification (IIAC; OMIM 208000) is characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. We analyzed affected individuals from 11 unrelated kindreds and found that IIAC was associated with mutations that inactivated ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). This cell surface enzyme generates inorganic pyrophosphate (PP(i)), a solute that regulates cell differentiation and serves as an essential physiologic inhibitor of calcification.