Functional analysis of cytoplasmic dynein in Caenorhabditis elegans has revealed a wide range of cellular functions for this minus-end-directed motor protein. Dynein transports a variety of cargos to diverse cellular locations, and thus cargo selection and destination are likely regulated by accessory proteins. The microtubule-associated proteins LIS-1 and dynein interact, but the nature of this interaction remains poorly understood. Here we show that both LIS-1 and the dynein heavy-chain DHC-1 are required for integrity of the actin cytoskeleton in C. elegans. Although both dhc-1(or195ts) and lis-1 loss-of-function disrupt the actin cytoskeleton and produce embryonic lethality, a double mutant suppresses these defects. A targeted RNA interference screen revealed that knockdown of other actin regulators, including actin-capping protein genes and prefoldin subunit genes, suppresses dhc-1(or195ts)-induced lethality. We propose that release or relocation of the mutant dynein complex mediates this suppression of dhc-1(or195ts)-induced phenotypes. These results reveal an unexpected direct or indirect interaction between the actin cytoskeleton and dynein activity.
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[Show abstract][Hide abstract]ABSTRACT: In Drosophila, like in humans, Dystrophin Glycoprotein Complex (DGC) deficiencies cause a life span shortening disease, associated with muscle dysfunction. We performed the first in vivo genetic interaction screen in ageing dystrophic muscles and identified genes that have not been shown before to have a role in the development of muscular dystrophy and interact with dystrophin and/or dystroglycan. Mutations in many of the found interacting genes cause age-dependent morphological and heat-induced physiological defects in muscles, suggesting their importance in the tissue. Majority of them is phylogenetically conserved and implicated in human disorders, mainly tumors and myopathies. Functionally they can be divided into three main categories: proteins involved in communication between muscle and neuron, and interestingly, in mechanical and cellular stress response pathways. Our data show that stress induces muscle degeneration and accelerates age-dependent muscular dystrophy. Dystrophic muscles are already compromised; and as a consequence they are less adaptive and more sensitive to energetic stress and to changes in the ambient temperature. However, only dystroglycan, but not dystrophin deficiency causes extreme myodegeneration induced by energetic stress suggesting that dystroglycan might be a component of the low-energy pathway and act as a transducer of energetic stress in normal and dystrophic muscles.
[Show abstract][Hide abstract]ABSTRACT: Nurses counsel the parents of patients leaving without being seen by a physician (LWBS) about common childhood illnesses. This strategy's impact is not known.
To assess the impact of nurse counseling on ED return visits and outcomes for children who LWBS.
This retrospective cohort study used the computerized database of a tertiary care pediatric ED. Participants were all triaged children who LWBS between April 1st 2008 and March 31st 2009. Parents who notified nurses of their intention to leave received information and counseling on when to return. This counseling's occurence was this study's exposure of interest. The control group included patients who LWBS without notification and thus were not counseled. The primary outcome was a return visit to the ED within 48h. Triage level and referral status were used as severity indicators. To demonstrate a 2% difference in return visits (α value 0.05, power 80%), 3213 participants were needed per group.
During the study period, 60,525 patients consulted the ED and 10,323 LWBS; of these, 4639 (45%) received nurse counseling and 5684 (65%) did not. There was a 2.0% (95% CI 1.0, 3.0) decrease in ED return visit proportions between groups. On multiple logistic regression, the counseled group was less likely to return to the ED within 48h.
This study suggests that, of patients who LWBS, those who receive counseling by a nurse have less return visits in the following 48h.
No preview · Article · Oct 2011 · International emergency nursing
[Show abstract][Hide abstract]ABSTRACT: Background
Essential genes are critical for the development of all organisms and are associated with many human diseases. These genes have been a difficult category to study prior to the availability of balanced lethal strains. Despite the power of targeted mutagenesis, there are limitations in identifying mutations in essential genes. In this paper, we describe the identification of coding regions for essential genes mutated using forward genetic screens in Caenorhabditis elegans. The lethal mutations described here were isolated and maintained by a wild-type allele on a rescuing duplication.
We applied whole genome sequencing to identify the causative molecular lesion resulting in lethality in existing C. elegans mutant strains. These strains are balanced and can be easily maintained for subsequent characterization. Our method can be effectively used to analyze mutations in a large number of essential genes. We describe here the identification of 64 essential genes in a region of chromosome I covered by the duplication sDp2. Of these, 42 are nonsense mutations, six are splice signal mutations, one deletion, and 15 are non-synonymous mutations. Many of the essential genes in this region function in cell cycle, transcriptional regulation, and RNA processing.
The essential genes identified here are represented by mutant strains, many of which have more than one mutant allele. The genetic resource can be utilized to further our understanding of essential gene function and will be applicable to the study of C. elegans development, conserved cellular function, and ultimately lead to improved human health.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-361) contains supplementary material, which is available to authorized users.