The meiotically expressed Zip3 protein is found conserved from Saccharomyces cerevisiae to humans. In baker's yeast, Zip3p has been implicated in synaptonemal complex (SC) formation, while little is known about the protein's function in multicellular organisms. We report here the successful targeted gene disruption of zhp-3 (K02B12.8), the ZIP3 homolog in the nematode Caenorhabditis elegans. Homozygous zhp-3 knockout worms show normal homologue pairing and SC formation. Also, the timing of appearance and the nuclear localization of the recombination protein Rad-51 seem normal in these animals, suggesting proper initiation of meiotic recombination by DNA double-strand breaks. However, the occurrence of univalents during diplotene indicates that C. elegans ZHP-3 protein is essential for reciprocal recombination between homologous chromosomes and thus chiasma formation. In the absence of ZHP-3, reciprocal recombination is abolished and double-strand breaks seem to be repaired via alternative pathways, leading to achiasmatic chromosomes and the occurrence of univalents during meiosis I. Green fluorescent protein-tagged C. elegans ZHP-3 forms lines between synapsed chromosomes and requires the SC for its proper localization.Most meiotic recombination is likely to depend on recombinational repair of programmed meiotic DNA double-strand breaks (DSBs), which are induced by Spo11p (6,19). In the budding yeast Saccharomyces cerevisiae, the fungus Coprinus cinereus, the mouse, and the flowering plant Arabidopsis thaliana, it was shown that this or an additional function of Spo11p is also required for the formation of the synaptonemal complex (SC), the proteinaceous structure that intimately links homologous chromosomes in meiotic prophase (2,17,25,28,34). C. elegans and Drosophila melanogaster are different in that Spo11p is dispensable for the initiation of SC formation (12,26). For the budding yeast S. cerevisiae, it was proposed that synapsis initiates at DSB sites (9), specifically those which are destined to become crossovers (1, 18). The protein Zip3 would mark these sites and recruit Zip2 and Zip1, the latter being the major component of the SC's central region (1, 16).In S. cerevisiae, a null mutation in ZIP3 leads to a two-to threefold reduction in crossovers (1). Moreover, DSBs accumulate in this mutant, indicating a defect in the normal progression of recombination (7). ZIP3 is a member of the group of ZMM genes, which all confer similar mutant phenotypes. The ZMM genes have been implicated in the progression of meiosis from crossover-destined DSBs to subsequent steps (single-end invasion, double Holliday junction) on the way to crossing over and SC nucleation, possibly by coordinating the biochemical processes with the formation of underlying chromosome structures (7).A C. elegans protein homologous to Zip3p (Cst9p), K02B12.8p (www.wormbase.org), was assigned a meiotic function by producing a weak Him phenotype in a large-scale RNA interference (RNAi) screen (15). Moreover, its expression was found to be enhanc...

This study demonstrates recombinative generalization of within-syllable units in prereading children. Three kindergarten children learned to select printed consonant-vowel-consonant words upon hearing the corresponding spoken words. The words were taught in sets; there were six sets, presented consecutively. Within sets, the four words that were taught had overlapping letters, for example, sat, mat, sop, and sug. Tests for recombinative generalization determined whether the children selected novel words with the same components as the trained words (e.g., mop and mug). Two children demonstrated recombinative generalization after one training set, and the 3rd demonstrated it after two training sets. In contrast, 2 other children, who received tests but no training, showed low accuracy across six sets. The 3 experimental children then demonstrated highly accurate printed-word-to-picture matching, and named the majority of the printed words. These findings are a promising step in the development of a computerized instructional technology for reading.DESCRIPTORS: recombinative generalization, reading, arbitrary matching to sample, childrenEstimates of the proportion of the U.S. population with reading difficulties range from 20% to 40% (Good, Simmons, & Smith, 1998;Stedman & Kaestle, 1987). Kameenui (1996) estimated that one in six children in Grades 1 through 3 have reading difficulties. Reading is a complex skill with numerous interrelated and interacting elements. As Adams (1990) ''unless the processes involved in individual word recognition operate properly, nothing else in the system can either'' (p. 3). When these foundational word naming 1 processes are operating properly, words that are composed of new combinations of previously learned letters and sounds are named the first time they are seen.The demonstration of novel recombinations of previously established linguistic units has been termed recombinative generalization (H. Goldstein, 1993). The recombinative generalization literature has shown that persons taught to respond to several different complex stimuli that contain overlapping units come to respond appropriately to different combinations of the same units (H. 1 We will use the phrase word naming to refer to seeing a printed word and saying the word. In so doing, we avoid using the comprehensive term reading for this single component of reading.

Phosphorylation of membrane proteins is a central regulatory and signaling mechanism across cell compartments. However, the recognition process and phosphorylation mechanism of membrane-bound substrates by kinases are virtually unknown. cAMP-dependent protein kinase A (PKA) is a ubiquitous enzyme that phosphorylates several soluble and membrane-bound substrates. In cardiomyocytes, PKA targets phospholamban (PLN), a membrane protein that inhibits the sarcoplasmic reticulum Ca2+-ATPase (SERCA). In the unphosphorylated state, PLN binds SERCA, reducing the calcium uptake and generating muscle contraction. PKA phosphorylation of PLN at S16 in the cytoplasmic helix relieves SERCA inhibition, initiating muscle relaxation. Using steady state kinetic assays, NMR spectroscopy, and molecular modeling we show that PKA recognizes and phosphorylates the excited, membrane detached R state of PLN. By promoting PLN from a ground state to excited state, we obtained a linear relationship between rate of phosphorylation and population of the excited state of PLN. The conformational equilibrium of PLN is crucial to regulate the extent of PLN phosphorylation as well as SERCA inhibition.

Light-dependent sensory responses in motile eubacteria were first discovered by Engelmann (1, 2). He observed that motile cells of Bacterium photometricum reversed the direction of movement when entering a dark zone. Photostimuli control swimming behavior in the Archaeon Halobacterium salinarium by modulating the frequency of reversals. An increase in the intensity of blue light increases the probability of reversal, whereas decreases in the intensity suppress reversal probability. Green-red light intensity changes have the inverse effect: increases in intensity suppress, whereas decreases enhance 4.5 jo -4.8.

Stem-bulge RNAs (sbRNAs) are a group of small, functionally yet uncharacterized noncoding RNAs first described in C. elegans, with a few homologous sequences postulated in C. briggsae. In this study, we report on a comprehensive survey of this ncRNA family in the phylum Nematoda. Employing homology search strategies based on both sequence and secondary structure models and a computational promoter screen we identified a total of 240 new sbRNA homologs. For the majority of these loci we identified both promoter regions and transcription termination signals characteristic for pol-III transcripts. Sequence and structure comparison with known RNA families revealed that sbRNAs are homologs of vertebrate Y RNAs. Most of the sbRNAs show the characteristic Ro protein binding motif, and contain a region highly similar to a functionally required motif for DNA replication previously thought to be unique to vertebrate Y RNAs. The single Y RNA that was previously described in C. elegans, however, does not show this motif, and in general bears the hallmarks of a highly derived family member.