Copulation defective mutants of C. elegans

To identify genes involved in male copulatory behavior, we carried out an F2 clonal screen in a him-5 mutant background. We identified 20 mutations that affect male mating behavior without causing gross defects in morphology. ​ Male mating in C. elegans comprises at least five steps (Liu and Sternberg, 1995). (l) The male responds to the hermaphrodite by backing his tail along the length of the hermaphrodite, (2) he turns over or under her body before reaching the head or tail, (3) he locates the vulva with his tail, at which point he stops backing, (4) he inserts his spicules into the vulva, and (5) he transfers sperm. To study the genetic basis for male mating behavior, we are isolating and characterizing Copulation Defective (Cod) mutations. We screened for mutant strains defective in this behavior using the screen described by Hodgkin (1983). him-5(e1490) worms are mutagenized with ethyl methane sulfonate (EMS); 20 P0 L4 hermaphrodites are picked singly to Petri plates; ten F1 worms are picked per mutagenized P0; and ten F2 L4 hermaphrodites are singled per P0 and their male progeny tested for mating efficiency via a qualitative mating test (six males crossed with six unc-52(e444) hermaphrodites, which are paralyzed at adulthood (Brenner, 1974). Mutants with phenotypes that are likely to reduce mating efficiency in a non-specific manner (such as those causing an Unc, Dpy, or Lon phenotype) were discarded. Those strains that appear morphologically normal under the dissecting microscope yet fail to mate or mate at a very low efficiency (1-5% cross progeny compared to wild type) were screened under Nomarski optics for defects in male reproductive structures. We screened over 3000 haploid genomes, and picked over 100 strains with reproduction defects. Nineteen strains were successfully backcrossed, which represents about 25% of the total strains attempted. This result suggests that most strains harbor two or more mutations that contribute to the mating-deficiency defect. Preliminary analysis of behavior suggests that every major step in the wild-type mating pathway has at least one corresponding Cod mutation blocking the behavior, with several mutations blocking at the spicule insertion step. The screen also yielded morphological mutants, whose phenotypes include crumpled spicules, abnormal rays, and a gonad migration defect; some of these will be described elsewhere (Chamberlin & Sternberg; micropublication in preparation)

Mass Spectra of Supersymmetric Yang-Mills Theories in 1+1 Dimensions

Physical mass spectra of supersymmetric Yang-Mills theories in 1+1 dimensions are evaluated in the light-cone gauge with a compact spatial dimension. The supercharges are constructed and the infrared regularization is unambiguously prescribed for supercharges, instead of the light-cone Hamiltonian. This provides a manifestly supersymmetric infrared regularization for the discretized light-cone approach. By an exact diagonalization of the supercharge matrix between up to several hundred color singlet bound states, we find a rapidly increasing density of states as mass increases.Comment: LaTeX file, 32 page, 7 eps figure

Consumption caught in the cash nexus.

During the last thirty years, ‘consumption’ has become a major topic in the study of contemporary culture within anthropology, psychology and sociology. For many authors it has become central to understanding the nature of material culture in the modern world but this paper argues that the concept is, in British writing at least, too concerned with its economic origins in the selling and buying of consumer goods or commodities. It is argued that to understand material culture as determined through the monetary exchange for things - the cash nexus - leads to an inadequate sociological understanding of the social relations with objects. The work of Jean Baudrillard is used both to critique the concept of consumption as it leads to a focus on advertising, choice, money and shopping and to point to a more sociologically adequate approach to material culture that explores objects in a system of models and series, ‘atmosphere’, functionality, biography, interaction and mediation

Modulation of Heat Shock Transcription Factor 1 as a Therapeutic Target for Small Molecule Intervention in Neurodegenerative Disease

A yeast-based small molecule screen identifies a novel activator of human HSF1 and protein chaperone expression and which appears to alleviate the toxicity of protein misfolding diseases

Plasmodium falciparum Hep1 is required to prevent the self aggregation of PfHsp70-3

The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria

DNA glycosylases: in DNA repair and beyond

The base excision repair machinery protects DNA in cells from the damaging effects of oxidation, alkylation, and deamination; it is specialized to fix single-base damage in the form of small chemical modifications. Base modifications can be mutagenic and/or cytotoxic, depending on how they interfere with the template function of the DNA during replication and transcription. DNA glycosylases play a key role in the elimination of such DNA lesions; they recognize and excise damaged bases, thereby initiating a repair process that restores the regular DNA structure with high accuracy. All glycosylases share a common mode of action for damage recognition; they flip bases out of the DNA helix into a selective active site pocket, the architecture of which permits a sensitive detection of even minor base irregularities. Within the past few years, it has become clear that nature has exploited this ability to read the chemical structure of DNA bases for purposes other than canonical DNA repair. DNA glycosylases have been brought into context with molecular processes relating to innate and adaptive immunity as well as to the control of DNA methylation and epigenetic stability. Here, we summarize the key structural and mechanistic features of DNA glycosylases with a special focus on the mammalian enzymes, and then review the evidence for the newly emerging biological functions beyond the protection of genome integrity

EEF2 Analysis Challenges the Monophyly of Archaeplastida and Chromalveolata

BACKGROUND: Classification of eukaryotes provides a fundamental phylogenetic framework for ecological, medical, and industrial research. In recent years eukaryotes have been classified into six major supergroups: Amoebozoa, Archaeplastida, Chromalveolata, Excavata, Opisthokonta, and Rhizaria. According to this supergroup classification, Archaeplastida and Chromalveolata each arose from a single plastid-generating endosymbiotic event involving a cyanobacterium (Archaeplastida) or red alga (Chromalveolata). Although the plastids within members of the Archaeplastida and Chromalveolata share some features, no nucleocytoplasmic synapomorphies supporting these supergroups are currently known. METHODOLOGY/PRINCIPAL FINDINGS: This study was designed to test the validity of the Archaeplastida and Chromalveolata through the analysis of nucleus-encoded eukaryotic translation elongation factor 2 (EEF2) and cytosolic heat-shock protein of 70 kDa (HSP70) sequences generated from the glaucophyte Cyanophora paradoxa, the cryptophytes Goniomonas truncata and Guillardia theta, the katablepharid Leucocryptos marina, the rhizarian Thaumatomonas sp. and the green alga Mesostigma viride. The HSP70 phylogeny was largely unresolved except for certain well-established groups. In contrast, EEF2 phylogeny recovered many well-established eukaryotic groups and, most interestingly, revealed a well-supported clade composed of cryptophytes, katablepharids, haptophytes, rhodophytes, and Viridiplantae (green algae and land plants). This clade is further supported by the presence of a two amino acid signature within EEF2, which appears to have arisen from amino acid replacement before the common origin of these eukaryotic groups. CONCLUSIONS/SIGNIFICANCE: Our EEF2 analysis strongly refutes the monophyly of the Archaeplastida and the Chromalveolata, adding to a growing body of evidence that limits the utility of these supergroups. In view of EEF2 phylogeny and other morphological evidence, we discuss the possibility of an alternative eukaryotic supergroup