Patterns of ribosomal gene variation in elite commercial chicken pure line populations

The nucleolus organizer region (NOR) encodes the tandemly repeated 18S, 5.8S and 28S ribosomal (r) RNA genes. The NORs of broiler and layer commercial chicken pure lines were studied to establish the type and extent of genetic variation at this important locus. The parameters studied were gene copy number, repeat size, and diversity of NOR-types. The populations were organized into three groups for analysis including brown-egg broiler (13 lines), brown-egg layer (six lines), and white-egg layer (eight lines). The ribosomal gene copy number average of the white-egg layer populations was significantly lower (329 genes) than that of the brown-egg layers (372 genes); the brown-egg broiler ribosomal gene average was intermediate (350 genes). The white-egg layer populations exhibited a ribosomal repeat unit average size of 36 kb, significantly different from the brown-egg layer and brown-egg broiler average repeat unit size of 32.5 and 33.9 kb, respectively. NOR array size was similar among the three groups (6 mb). The brown-egg broiler populations exhibited polymorphic NOR patterns, intra- and interline, whereas the white-egg layer populations were essentially monomorphic for NOR-type; brown-egg layers exhibited an intermediate level of NOR diversity. Some NOR array characteristics may be a function of breed origin as brown-egg commercial populations, both broilers and layers, have similar breed origins and exhibited similarities for predominant repeat unit size as compared with white-egg layer populations. However, the finding that brown-egg broiler lines typically exhibit a greater number of segregating NOR-types than brown-egg layer lines suggests that the selection schemes of broiler vs. layer pure line populations may also have influenced the degree of variation at this gene complex.     

Neuronal glutamate transporters vary in substrate transport rate but not in unitary anion channel conductance

Excitatory amino acid transporters (EAATs) not only sustain a secondary active glutamate transport but also function as anion-selective ion channels. The relative proportion of currents generated by glutamate transport or by the chloride conductance varies for each cloned EAAT subtype. For EAAT1, EAAT2, and EAAT3, the anion current is only a small component of the total transporter-associated current amplitude, whereas EAAT4 and EAAT5 transporters mediate predominantly anion currents. We here demonstrate that the distinct current proportions are entirely due to differences in glutamate transport rates. EAAT3 and EAAT4 differ in unitary glutamate transport rates as well as in the voltage and substrate dependence of anion channel opening, but ion conduction properties are very similar. Noise analysis revealed identical unitary current amplitudes and similar absolute open probabilities for the two anion channels. The low glutamate transport rate of EAAT4 allows regulation of cellular excitability without interfering with extracellular glutamate homeostasis and makes this EAAT isoform ideally suited to regulate excitability in dendritic spines of Purkinje neurons.     

Aging in the colonial chordate,Botryllus schlosseri

What mechanisms underlie aging? One theory, the wear-and-tear model, attributes aging to progressive deterioration in the molecular and cellular machinery which eventually lead to death through the disruption of physiological homeostasis. The second suggests that life span is genetically programmed, and aging may be derived from intrinsic processes which enforce a non-random, terminal time interval for the survivability of the organism. We are studying an organism that demonstrates both properties: the colonial ascidian, Botryllus schlosseri. Botryllus is a member of the Tunicata, the sister group to the vertebrates, and has a number of life history traits which make it an excellent model for studies on aging. First, Botryllus has a colonial life history, and grows by a process of asexual reproduction during which entire bodies, including all somatic and germline lineages, regenerate every week, resulting in a colony of genetically identical individuals. Second, previous studies of lifespan in genetically distinct Botryllus lineages suggest that a direct, heritable basis underlying mortality exists that is unlinked to reproductive effort and other life history traits. Here we will review recent efforts to take advantage of the unique life history traits of B. schlosseri and develop it into a robust model for aging research.     

Synthesis and characterization of tritylthioethanamine derivatives with potent KSP inhibitory activity

Assembly of a bipolar mitotic spindle requires the action of class 5 kinesins, and inhibition or depletion of this motor results in mitotic arrest and apoptosis. S-Trityl-l-cysteine is an allosteric inhibitor of vertebrate Kinesin Spindle Protein (KSP) that has generated considerable interest due to its anti-cancer properties, however, poor pharmacological properties have limited the use of this compound. We have modified the triphenylmethyl and cysteine groups, guided by biochemical and cell-based assays, to yield new cysteinol and cysteamine derivatives with increased inhibitory activity, greater efficacy in model systems, and significantly enhanced potency against the NCI60 tumor panel. These results reveal a promising new class of conformationally-flexible small molecules as allosteric KSP inhibitors for use as research tools, with activities that provide impetus for further development as anti-tumor agents.