Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number

Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens

The effects of radiation on the density of an aluminoborosilicate glass

Glasses used for nuclear waste immobilization are subjected to high levels of radiation, and this may affect their physicochemical properties. Alpha radiation is responsible for an important fraction of the radiation energy dissipated in these glasses. It has been reported previously that some borosilicate glasses increase their density during irradiation while the density of other glasses decreases. Although the density increase of silica after irradiation has been understood, thanks mainly to molecular dynamics calculations and diffraction experiments, the processes involved in more complex glasses could be more varied. In this work we irradiated an aluminum-borosilicate glass which is a candidate for the aforementioned purposes and which increases density during alpha irradiation from the B-10 (n,alpha) Li-7 reaction. We studied the effects of alpha irradiation on its microstructure, using several experimental techniques, and subsequently correlated the results. Small angle X-ray scattering (SAXS) measurements revealed the presence of inhomogeneities of about 10 Angstrom in the untreated samples. After annealing these samples, TEM images displayed a contrast structure and helium pycnometry revealed density changes, both typical of glass phase separation. After irradiation, the glass density increased and the SAXS intensity decreased, indicating a compositional homogenization process in the samples subject to a higher dose of irradiation. Atomic displacements were calculated by means of the TRIM [1] computer code. The number of displacements produced by each 10B(n,alpha) Li-7 reaction was estimated at 580 and involved distances of up to 15 Angstrom An increase in the density of the irradiated samples can be explained in terms of the atomic displacements produced by the nuclear reaction cascades of the reaction B-10 (n,alpha) Li-7, in the scenario of pre-existing phase separation in the samples. In the case of the aluminum-borosilicate glasses studied here, which exhibit a fine phase separation, the density of the Si-rich phase increases with the incorporation of Na and B atoms. The B-rich phase also increases its density with the flow of Si atoms from the matrix. Vacancies created by irradiation in the glass structure, are responsible for a density decrease. The final effect is due to the sum of all contributions described, which in this case results in a net density increase of the irradiated samples. An understanding of this phenomenon can lead to the design of new glasses which overcome radiation with a minimum of density change. (C) 2001 Elsevier Science BY. All rights reserved.2894169917518

Identifying (non-)coding RNAs and small peptides: Challenges and opportunities

Over the past decade, high-throughput studies have identified many novel transcripts. While their existence is undisputed, their coding potential and functionality have remained controversial. Recent computational approaches guided by ribosome profiling have indicated that translation is far more pervasive than anticipated and takes place on many transcripts previously assumed to be non-coding. Some of these newly discovered translated transcripts encode short, functional proteins that had been missed in prior screens. Other transcripts are translated, but it might be the process of translation rather than the resulting peptides that serve a function. Here, we review annotation studies in zebrafish to discuss the challenges of placing RNAs onto the continuum that ranges from functional protein-encoding mRNAs to potentially non-functional peptide-producing RNAs to non-coding RNAs. As highlighted by the discovery of the novel signaling peptide Apela/ELABELA/Toddler, accurate annotations can give rise to exciting opportunities to identify the functions of previously uncharacterized transcripts