A Novel Mutation in the Upstream Open Reading Frame of the CDKN1B Gene Causes a MEN4 Phenotype

PubMed ID: 23555276This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Systematic discovery of unannotated genes in 11 yeast species using a database of orthologous genomic segments

<p>Abstract</p> <p>Background</p> <p>In standard BLAST searches, no information other than the sequences of the query and the database entries is considered. However, in situations where two genes from different species have only borderline similarity in a BLAST search, the discovery that the genes are located within a region of conserved gene order (synteny) can provide additional evidence that they are orthologs. Thus, for interpreting borderline search results, it would be useful to know whether the syntenic context of a database hit is similar to that of the query. This principle has often been used in investigations of particular genes or genomic regions, but to our knowledge it has never been implemented systematically.</p> <p>Results</p> <p>We made use of the synteny information contained in the Yeast Gene Order Browser database for 11 yeast species to carry out a systematic search for protein-coding genes that were overlooked in the original annotations of one or more yeast genomes but which are syntenic with their orthologs. Such genes tend to have been overlooked because they are short, highly divergent, or contain introns. The key features of our software - called SearchDOGS - are that the database entries are classified into sets of genomic segments that are already known to be orthologous, and that very weak BLAST hits are retained for further analysis if their genomic location is similar to that of the query. Using SearchDOGS we identified 595 additional protein-coding genes among the 11 yeast species, including two new genes in <it>Saccharomyces cerevisiae</it>. We found additional genes for the mating pheromone a-factor in six species including <it>Kluyveromyces lactis</it>.</p> <p>Conclusions</p> <p>SearchDOGS has proven highly successful for identifying overlooked genes in the yeast genomes. We anticipate that our approach can be adapted for study of further groups of species, such as bacterial genomes. More generally, the concept of doing sequence similarity searches against databases to which external information has been added may prove useful in other settings.</p

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Culturally responsive literacy practices in an early childhood community.

Early childhood educators continue to see an increase in their culturally diverse student population. As our country continues to grow as a multicultural nation, it is imperative that our early childhood classrooms embrace this rich diversity and provide experiences that affirm all students, families and communities. We (teacher educators) synthesized the current research into the following five frameworks that we believe embody the foundation of culturally responsive teaching (CRT) in an early childhood setting: (a) developing a culturally responsive classroom community, (b) family engagement, (c) critical literacy within a social justice framework, (d) multicultural literature, and (e) culturally responsive print rich environments. In this article we situate each framework within the larger context of research. Next we move beyond discussing CRT practices by offering ideas on how culturally responsive classrooms look and how to implement this pedagogy and in an early childhood setting with real classroom practices