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This Week in PNAS: Nov 21, 2012

In the early, online edition of the Proceedings of the National Academy of Sciences, a team from the US and Japan characterizes the relationship between two coral reef-associated organisms: the tropical, filter-feeding tunicate Lissoclinum patella and its alpha-proteobacterium symbiont, Candidatus Endolissoclinum faulkneri. Using metagenomic sequence data from tunicate samples sequenced using Roche 454, Illumina, or Sanger approaches, the researchers cobbled together a genome sequence for the bacterial symbiont. Though Ca. E. faulkneri appears to have jettisoned much of its sequence in favor of simplicity, they say, the genome still contains components of a pathway used to produce a set of secondary metabolites called patellazoles — believed to be important for the tunicate's chemical defense.

Researchers from Georgetown University Medical Center and the University of North Carolina describe a type of self-renewing cells called conditionally reprogrammed cells, or CRCs, that resemble — but have distinct features from — embryonic stem cells or induced pluripotent stem cells. The study follows from prior work showing that adult primary epithelial cells from mammals can be prompted into a stem-like state using a Rho kinase inhibitor and irradiated fibroblast cells. By characterizing the self-renewing CRCs further, the team found that these cells do not express the sorts of markers associated with eSCs or iPSCs. And the stem-like features of the CRCs are only maintained when the appropriate signals are present, researchers report, adding that "CRC markers revert completely upon removal of the reprogramming conditions, and the cells differentiate in a tissue-specific manner."

Finally, Cornell University's Hening Lin and colleagues describe the chemogenomic strategy used to find an unknown gene in an otherwise well-described biosynthesis pathway in the yeast model organism Saccharomyces cerevisiae. Using data for thousands of yeast deletion strains grown in different environmental conditions and chemical exposures, the team tracked down a gene called YLR143W that encodes diphthamide synthetase, an enzyme involved in the final step of a pathway leading to the production of a compound called diphthamide. "We discovered diphthamide synthetase, the enzyme that has remained unknown for more than 30 years after the diphthamide structure was determined ... by grouping the co-fitness values of all known diphthamide biosynthetic genes," the study's authors write.

The Scan

Expanded Genetic Testing Uncovers Hereditary Cancer Risk in Significant Subset of Cancer Patients

In Genome Medicine, researchers found pathogenic or likely pathogenic hereditary cancer risk variants in close to 17 percent of the 17,523 patients profiled with expanded germline genetic testing.

Mitochondrial Replacement Therapy Embryos Appear Largely Normal in Single-Cell 'Omics Analyses

Embryos produced with spindle transfer-based mitochondrial replacement had delayed demethylation, but typical aneuploidy and transcriptome features in a PLOS Biology study.

Cancer Patients Report Quality of Life Benefits for Immune Checkpoint Inhibitors

Immune checkpoint inhibitor immunotherapy was linked in JAMA Network Open to enhanced quality of life compared to other treatment types in cancer patients.

Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

Investigators find a diagnostic edge for whole-genome sequencing, while highlighting the cost advantages and improving diagnostic rate of exome sequencing in EJHG.