[
Front Genet,
2019]
Onchocerciasis and lymphatic filariasis are targeted for elimination, primarily using mass drug administration at the country and community levels. Elimination of transmission is the onchocerciasis target and global elimination as a public health problem is the end point for lymphatic filariasis. Where program duration, treatment coverage, and compliance are sufficiently high, elimination is achievable for both parasites within defined geographic areas. However, transmission has re-emerged after apparent elimination in some areas, and in others has continued despite years of mass drug treatment. A critical question is whether this re-emergence and/or persistence of transmission is due to persistence of local parasites-i.e., the result of insufficient duration or drug coverage, poor parasite response to the drugs, or inadequate methods of assessment and/or criteria for determining when to stop treatment-or due to re-introduction of parasites <i>via</i> human or vector movement from another endemic area. We review recent genetics-based research exploring these questions in <i>Onchocerca volvulus</i>, the filarial nematode that causes onchocerciasis, and <i>Wuchereria bancrofti</i>, the major pathogen for lymphatic filariasis. We focus in particular on the combination of genomic epidemiology and genome-wide associations to delineate transmission zones and distinguish between local and introduced parasites as the source of resurgence or continuing transmission, and to identify genetic markers associated with parasite response to chemotherapy. Our ultimate goal is to assist elimination efforts by developing easy-to-use tools that incorporate genetic information about transmission and drug response for more effective mass drug distribution, surveillance strategies, and decisions on when to stop interventions to improve sustainability of elimination.
[
Trends Genet,
1998]
Studies of sex myoblast (SM) migration in the nematode Caenorhabditis elegans have shown that multiple guidance mechanisms cooperate to ensure the accurate and reproducible targeting of the SMs. Many issues arise in the analysis of SM migration, including the action of multiple guidance mechanisms, redundant sources of guidance information, the multiple uses of molecular components, and whether factors affect cell fate determination events or the guidance mechanisms themselves. These issues are common to many cell migration events and make the analysis of SM migration instructive to our general understanding of how cell migrations are controlled.
[
J Cell Sci,
2002]
The canonical UCS (UNC-45/Crol/She4p) protein, Caenorhabditis elegans UNC-45, was one of the earliest molecules to be shown genetically to be necessary for sarcomere assembly. Genetic analyses of homologues in several fungal species indicate that the conserved UCS domain functionally interacts with conventional type II and unconventional type V myosins. In C. elegans and other invertebrate species, UNC-45 and its orthologues interact with both sarcomeric and non-sarcomeric myosins whereas, in vertebrates, there are two UNC-45 isoforms: a general cell (GC) and a striated muscle (SM) isoform. Although the mechanism of action of UCS proteins is unknown, recent biochemical studies suggest that they may act as molecular chaperones that facilitate the folding and/or maturation of myosin.
[
RNA Biol,
2009]
SmY RNAs are a family of approximately 70-90 nt small nuclear RNAs found in nematodes. In C. elegans, SmY RNAs copurify in a small ribonucleoprotein (snRNP) complex related to the SL1 and SL2 snRNPs that are involved in nematode mRNA trans-splicing. Here we describe a comprehensive computational analysis of SmY RNA homologs found in the currently available genome sequences. We identify homologs in all sequenced nematode genomes in class Chromadorea. We are unable to identify homologs in a more distantly related nematode species, Trichinella spiralis (class: Dorylaimia), and in representatives of non-nematode phyla that use trans-splicing. Using comparative RNA sequence analysis, we infer a conserved consensus SmY RNA secondary structure consisting of two stems flanking a consensus Sm protein binding site. A representative seed alignment of the SmY RNA family, annotated with the inferred consensus secondary structure, has been deposited with the Rfam RNA families database.