Ebert RHA et al. (1996) Dev Genet "Defining genes that govern longevity in Caenorhabditis elegans."

Sohal BH, Egilmez NK, Ebert RHA, Shmookler Reis RJ, Shammas MA, Ruggles S, Sohal RS

[Dev Genet, 1996]

We previously identified five regions on the chromosomal map of Caenorhabditis elegans, containing genes that help specify life span in this species, by comparing the genotypes of young and long-lived progeny from a cross between strains Bristol-N2 and Bergerac-BO [Ebert et al. (1993): Genetics 135:1003-1010]. Analyses of additional crosses, and of putative polymorphisms for the implicated genes, are necessary to clarify the roles of naturally occurring polymorphic alleles in determining longevity. We therefore carried out a second multigenerational cross, between strains Bristol-N2 and DH424 (both nonmutators at 20 degrees C), to create a different heterogeneous recombinant-inbred population. We again found strong evidence implicating multiple genes, which differ between the parental strains, in the determination of life span. Increased variance of survival, for F2 and homozygous F25 worms relative to F1 hybrids, is consistent with such alleles assorting randomly in the cross progeny. Moreover, chromosome mapping data corroborate the polygenic nature of this quantitative trait. Genotypes of young and very long-lived adult worms from a synchronous F15 population were determined by polymerase chain reaction, to identify the parental strain of origin for each of 10 polymorphic loci. Two regions, on chromosomes II and IV, each contain at least one gene with allelic differences in associated longevity. A recombinant-inbred Bergerac-BO x Bristol-N2 population, derived from the earlier cross between those strains, was exposed to an acute toxic level of hydrogen peroxide. Genotyping of H2O2-resistant worms implicated at least one of the five chromosomal regions previously identified in the same cross progeny as harboring a longevity-determining gene. Superoxide dismutase and catalase levels, determined for the three parental strains as they aged, confirm the existence of polymorphisms in the corresponding genes (or their regulatory mechanisms) inferred from the chromosome-II mapping data, and are consistent with the hypothesis that increased longevity is conferred by high levels of these enzymes late in life.

Lama D et al. (2010) Biochemistry "Identification of core structural residues in the sequentially diverse and structurally homologous Bcl-2 family of proteins."

Lama D, Sankararamakrishnan R

[Biochemistry, 2010]

The Bcl-2 family of proteins regulates the intrinsic pathway of apoptosis and plays a significant role in mitochondrial outer membrane permeabilization. Bcl-2 homologues belonging to both anti- and pro-apoptotic classes have been identified in diverse organisms. While anti-apoptotic Bcl-2 proteins possess up to four BH sequence domains (BH1-BH4), the pro-apoptotic counterparts have either three BH (BH1-BH3) domains or only the BH3 domain. Many anti-apoptotic viral homologues do not seem to have any detectable BH homology regions and exhibit a very low level of sequence identity with other Bcl-2 family members. However, structures determined for several Bcl-2 anti- and pro-apoptotic proteins and their viral homologues show a remarkably conserved helical fold characterized by a central hydrophobic helix surrounded by five or six amphipathic helices. In this study, we have analyzed 16 nonredundant Bcl-2 structures from human, mouse, Caenorhabditis elegans, and five different viral species. While the length of the central hydrophobic helix is preserved in all the Bcl-2 structures, variations in length are observed for other helices. We performed multiple-structure alignment of all 16 structures. Eighty structurally equivalent positions, the bulk of them in the helical regions, constituted the ungapped blocks in the structure-based sequence alignment. Analysis of helix bundle geometry indicates that helix-helix packing differed in different Bcl-2 structures. This is presumably to accommodate disparate residue substitutions. Residue properties such as solvent accessibility, conservation of chemical nature, and/or size and involvement in interhelical interactions were analyzed in each position of the ungapped alignment regions. A sequence motif made up of small amino acids has been detected in the central helix that is proposed to be important for helix-helix association. We have found that residues in 22 positions in the helical regions are buried, exhibit conservation in hydrophobicity and/or size, and participate in interhelical interactions in at least 12 of the 16 structures studied. We also found 15 additional positions in which residues exhibit two of the three properties investigated. We suggest that these positions constitute the important structural core in the diverse Bcl-2 family members and could play a significant role in the folding of the protein. Results of our studies have been used in the identification of three putative Bcl-2 homologues from three different viral organisms. This study will help in the genome-wide identification of hitherto unrecognized Bcl-2 family members, especially in viral genomes.

Ramki K et al. (2023) Methods "An aggregation-induced emission-based ratiometric fluorescent chemosensor for Hg(II) and its application in Caenorhabditis elegans imaging."

Ramasamy SK, Ramki K, Sakthivel P, Sundararaj P, Thiruppathi G

[Methods, 2023]

A chromone-based ratiometric fluorescent probe L2 was developed for the selective detection of Hg(II) in a semi-aqueous solution based on aggregation-induced emission (AIE) and chelation-enhanced fluorescence (CHEF) effect. The probe L2 fluoresced significantly at 498 nm in its aggregated state, and when chelated with Hg(II), the soluble state fluoresced 1-fold higher. In addition, Job's plot reveals that the probe forms a 1:1 stoichiometry complex with Hg(II) with an association constant of 9.1 × 10³M^-1 estimated by the BH plot. The probe L2 detects Hg(II) down to 22.47 nM without interference from other interfering ions. The FTIR, ESI mass, and DFT-based computational studies investigated the binding mechanism of probe L2 with Hg(II). Taking advantage of its AIE characteristics, the probe L2 was successfully applied for bio-capability analysis in Caenorhabditis elegans (a nematode worm) imaging of Hg(II) in a living model.