Studies examining factors that influence when words are learned typically investigate one lexical category or a small set of words. We provide the first evaluation of the relation between input frequency and age of acquisition for a large sample of words. The MacArthur-Bates Communicative Development Inventory provides norming data on age of acquisition for 562 individual words collected from the parents of children aged 0 ; 8 to 2 ; 6. The CHILDES database provides estimates of frequency with which parents use these words with their children (age: 0 ; 7-7 ; 5; mean age: 36 months). For production, across all words higher parental frequency is associated with later acquisition. Within lexical categories, however, higher frequency is related to earlier acquisition. For comprehension, parental frequency correlates significantly with the age of acquisition only for common nouns. Frequency effects change with development. Thus, frequency impacts vocabulary acquisition in a complex interaction with category, modality and developmental stage.
Feldman et al. criticize the MacArthur Communicative Development Inventories (CDIs) as having too much variability, too little stability, and insufficient ability to predict early language delay. We present data showing that these characteristics of the CDI are authentic reflections of individual differences in early language development rather than measurement deficiencies. We also respond to their critical assertions concerning sociodemographic influences on the CDI scores.
Antibodies are key reagents in biology and medicine, but commercial sources are rarely recombinant and thus do not provide a permanent and renewable resource. Here, we describe an industrialized platform to generate antigens and validated recombinant antibodies for 346 transcription factors (TFs) and 211 epigenetic antigens. We describe an optimized automated phage display and antigen expression pipeline that in aggregate produced about 3000 sequenced Fragment antigen-binding domain that had high affinity (typically EC50<20 nm), high stability (Tm∼80 °C), good expression in E. coli (∼5 mg/L), and ability to bind antigen in complex cell lysates. We evaluated a subset of Fabs generated to homologous SCAN domains for binding specificities. These Fragment antigen-binding domains were monospecific to their target SCAN antigen except in rare cases where they cross-reacted with a few highly related antigens. Remarkably, immunofluorescence experiments in six cell lines for 270 of the TF antigens, each having multiple antibodies, show that ∼70% stain predominantly in the cytosol and ∼20% stain in the nucleus which reinforces the dominant role that translocation plays in TF biology. These cloned antibody reagents are being made available to the academic community through our web site recombinant-antibodies.org to allow a more system-wide analysis of TF and chromatin biology. We believe these platforms, infrastructure, and automated approaches will facilitate the next generation of renewable antibody reagents to the human proteome in the coming decade.
In recent years, DNA vaccines have undergone a number of technological advancements that have incited renewed interest and heightened promise in the field. Two such improvements are the use of genetically engineered cytokine adjuvants and plasmid delivery via in vivo electroporation (EP), the latter of which has been shown to increase antigen delivery by nearly 1000-fold compared to naked DNA plasmid delivery alone. Both strategies, either separately or in combination, have been shown to augment cellular and humoral immune responses in not only mice, but also in large animal models. These promising results, coupled with recent clinical trials that have shown enhanced immune responses in humans, highlight the bright prospects for DNA vaccines to address many human diseases.
Three studies assessed the ability of 2-year-olds to use semantic context to infer the meanings of novel nouns and to retain those meanings a day later. In the first experiment, 24 2-year-olds heard novel nouns in sentences that contained semantically constraining verbs (e.g., "Mommy feeds the ferret"). They chose from a set of four novel object pictures to indicate the referent. Children learned a majority of the novel words. However, they occasionally failed to choose the correct object even when they understood the verb. Experiment 2 examined whether this was due to an inability to identify some of the pictures of novel objects. Experiment 3 tested 24 2-year-olds' memory for the newly learned nouns following a 24 hr delay and found significant retention. Results are discussed in terms of learning mechanisms that facilitate vocabulary acquisition in young children.
Production of healthy gametes in meiosis relies on the quality control and proper distribution of both nuclear and cytoplasmic contents. Meiotic differentiation naturally eliminates age-induced cellular damage by an unknown mechanism. Using time-lapse fluorescence microscopy in budding yeast, we found that nuclear senescence factors – including protein aggregates, extrachromosomal ribosomal DNA circles, and abnormal nucleolar material – are sequestered away from chromosomes during meiosis II and subsequently eliminated. A similar sequestration and elimination process occurs for the core subunits of the nuclear pore complex in both young and aged cells. Nuclear envelope remodeling drives the formation of a membranous compartment containing the sequestered material. Importantly, de novo generation of plasma membrane is required for the sequestration event, preventing the inheritance of long-lived nucleoporins and senescence factors into the newly formed gametes. Our study uncovers a new mechanism of nuclear quality control and provides insight into its function in meiotic cellular rejuvenation.
Histone chaperones are proteins that interact with histones to regulate the thermodynamic process of nucleosome assembly. sNASP and ASF1 are conserved histone chaperones that interact with histones H3 and H4 and are found in a multi-chaperoning complex in vivo. Previously we identified a short peptide motif within H3 that binds to the TPR domain of sNASP with nanomolar affinity. Interestingly, this peptide motif is sequestered within the known ASF1–H3–H4 interface, raising the question of how these two proteins are found in complex together with histones when they share the same binding site. Here, we show that sNASP contains at least two additional histone interaction sites that, unlike the TPR–H3 peptide interaction, are compatible with ASF1A binding. These surfaces allow ASF1A to form a quaternary complex with both sNASP and H3–H4. Furthermore, we demonstrate that sNASP makes a specific complex with H3 on its own in vitro, but not with H4, suggesting that it could work upstream of ASF1A. Further, we show that sNASP and ASF1A are capable of folding an H3–H4 dimer in vitro under native conditions. These findings reveal a network of binding events that may promote the entry of histones H3 and H4 into the nucleosome assembly pathway.
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