Uncovering New Functions for MicroRNAs in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e

In the race to understand microRNA (miRNA) functions in development and physiology, Caenorhabditis elegans investigators were the first out of the gate with the cloning and analysis of the lin-4 and let-7 miRNAs [1,2]. The starting point of strong, penetrant loss of function phenotypes facilitated these advancements. However, subsequent functional analysis of miRNAs in C. elegans was hampered by the lack of easily observable loss-of-function phenotypes [3]. There are several possible models to account for this observation. First, redundancy between related miRNAs can account for the absence of phenotypes in mutants missing individual miRNA genes [4,5]. Second, miRNAs may also function redundantly with unrelated miRNAs or other regulatory mechanisms. Third, identification of miRNA functions may require the analysis of specific cells during development, assays typically not included in initial broad phenotypic analyses. For example, the lsy-6 miRNA is an essential regulator of a chemosensory neuron cell fate in C. elegans [6]. Such a specialized function would not have been identified in broad phenotypic analyses. Finally, miRNAs may act to ‘fine-tune’ gene expression, to maintain protein levels of targets in an optimal range. Loss of this relatively minor regulatory input by miRNAs would not be expected to result in penetrant, observable defects under normal conditions. Recent work has analyzed the functions of individual miRNAs under conditions of environmental or physiological stress. With these approaches, functions for individual miRNAs, which remain elusive under normal growth conditions, have been uncovered. These stresses can be introduced through genetic mutations, environmental perturbations, or through the normal aging process. These results are consistent with the hypothesis that miRNAs act to ensure the robustness of developmental or physiological pathways [7]

Video-Based Information Systems in Academic Library Media Centers

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Future Summary

We are emerging from a period of consolidation in particle physics. Its great, historic achievement was to establish the Theory of Matter. This Theory will serve as our description of ordinary matter under ordinary conditions -- allowing for an extremely liberal definition of "ordinary -- for the foreseeable future. Yet there are many indications, ranging from the numerical to the semi-mystical, that a new fertile period lies before us. We will discover compelling evidence for the unification of fundamental forces and for new quantum dimensions (low-energy supersymmetry). We will identify new forms of matter, which dominate the mass density of the Universe. We will achieve much better fundamental understanding of the behavior of matter in extreme astrophysical and cosmological environments. Lying beyond these expectations, we can identify deep questions that seem to call for ideas outside our present grasp. And there's still plenty of room for surprises.Comment: 25 pages, 13 EPS figures, LaTeX with BoxedEPS macros. Closing talk delivered at the LEPfest, CERN, October 11, 2000. Email correspondence to [email protected]

Test experience on an ultrareliable computer communication network

The dispersed sensor processing mesh (DSPM) is an experimental, ultra-reliable, fault-tolerant computer communications network that exhibits an organic-like ability to regenerate itself after suffering damage. The regeneration is accomplished by two routines - grow and repair. This paper discusses the DSPM concept for achieving fault tolerance and provides a brief description of the mechanization of both the experiment and the six-node experimental network. The main topic of this paper is the system performance of the growth algorithm contained in the grow routine. The characteristics imbued to DSPM by the growth algorithm are also discussed. Data from an experimental DSPM network and software simulation of larger DSPM-type networks are used to examine the inherent limitation on growth time by the growth algorithm and the relationship of growth time to network size and topology

Social and democratic participation in residential settings for older people: realities and aspiration

This paper explores some of the experiences of older people living in residential settings (sheltered, very sheltered housing and residential care), in the context of theories of participation, consumerism and citizenship. It draws on material from personal interviews undertaken with over 100 older people in England and Wales, and also from discussions with staff. Two-thirds of respondents were aged over 85. A significant minority of residents expressed some concerns about the routines of life, such as meals and social contact. Staff expectations of social participation were often unrealistic : for many residents, social contact was more a matter of adjustment than of friendship. Residents did not participate in deciding how the residential settings where they lived should be organised and managed, except for helping with simple domestic tasks. There is a need to change both attitudes and practice to enable older people to participate more fully in these settings

The \u3cem\u3emir-51\u3c/em\u3e Family of MicroRNAs Functions in Diverse Regulatory Pathways in \u3cem\u3eCaenorhbditis elegans\u3c/em\u3e

The mir-51 family of microRNAs (miRNAs) in C. elegans are part of the deeply conserved miR-99/100 family. While loss of all six family members (mir-51-56) in C. elegans results in embryonic lethality, loss of individual mir-51 family members results in a suppression of retarded developmental timing defects associated with the loss of alg-1. The mechanism of this suppression of developmental timing defects is unknown. To address this, we characterized the function of the mir-51 family in the developmental timing pathway. We performed genetic analysis and determined that mir-51 family members regulate the developmental timing pathway in the L2 stage upstream of hbl-1. Loss of the mir-51 family member, mir-52, suppressed retarded developmental timing defects associated with the loss of let-7 family members and lin-46. Enhancement of precocious defects was observed for mutations in lin-14, hbl-1, and mir-48(ve33), but not later acting developmental timing genes. Interestingly, mir-51 family members showed genetic interactions with additional miRNA-regulated pathways, which are regulated by the let-7 and mir-35 family miRNAs, lsy-6, miR-240/786, and miR-1. Loss of mir-52 likely does not suppress miRNA-regulated pathways through an increase in miRNA biogenesis or miRNA activity. We found no increase in the levels of four mature miRNAs, let-7, miR-58, miR-62 or miR-244, in mir-52 or mir-52/53/54/55/56 mutant worms. In addition, we observed no increase in the activity of ectopic lsy-6 in the repression of a downstream target in uterine cells in worms that lack mir-52. We propose that the mir-51 family functions broadly through the regulation of multiple targets, which have not yet been identified, in diverse regulatory pathways in C. elegans

The Background Field Method as a Canonical Transformation

We construct explicitly the canonical transformation that controls the full dependence (local and non-local) of the vertex functional of a Yang-Mills theory on a background field. After showing that the canonical transformation found is nothing but a direct field-theoretic generalization of the Lie transform of classical analytical mechanics, we comment on a number of possible applications, and in particular the non perturbative implementation of the background field method on the lattice, the background field formulation of the two particle irreducible formalism, and, finally, the formulation of the Schwinger-Dyson series in the presence of topologically non-trivial configurations.Comment: 11 pages, REVTeX. References added, some explanations extended. Final version to appear in the journa