In the PNAS Early Edition this week, Cold Spring Harbor Laboratory's Scott Lowe and his colleagues "demonstrate the feasibility of transgenic inducible RNAi for suppression of essential genes." In an adult mouse model, Lowe's team targeted cell proliferation by screening an RNAi library against DNA replication factors; the group identified multiple short hairpin RNAs against Replication Protein A, subunit 3 — RPA3 — and, subsequently, "generated transgenic mice with TRE-driven Rpa3 shRNAs whose expression enforced a reversible cell cycle arrest," it writes. While blocking cell proliferation "caused rapid atrophy of the intestinal epithelium which led to weight loss and lethality within 8 to 11 [days]," the team found it could reverse villus atrophy and weight loss by withdrawing the short hairpin RNAs. Overall, Lowe et al. say that their "shRpa3 transgenic mice provide an interesting tool to study tissue maintenance and regeneration," and that their method opens a door to further studies of "inducible and reversible suppression of essential genes in a mammalian system."
A team led by investigators at the Georgia Institute of Technology reports genome sequences for nine environmentally adapted strains of E. coli that are "phenotypically and taxonomically indistinguishable" from the commensal or pathogenic forms of the bacterium. The commensal E. coli genomes, the team writes, "encode for more functions that are important for fitness in the human gut, do not exchange genetic material with their environmental counterparts, and hence do not evolve according to the recently proposed fragmented speciation model." The team says that its findings "have important implications for reliable diagnosis and regulation of pathogenic E. coli and for the coliform cell-counting test."
The Fred Hutchinson Cancer Research Center's Chen Yanover and Philip Bradley present their analysis of the size and sequence diversity of class I major histocompatibility complex protein structure-based binding landscapes. From this, they were able to "identify subtle patterns of covariation between peptide sequence positions." Based on structural models associated with these binding landscapes, Yanover and Bradley say that "physical interactions that may mediate these sequence correlations."
Researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, along with their international colleagues, report in PNAS this week that the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis — PFAPA, the most common periodic fever disease in children — may be a result of environmentally triggered IL-1β activation. In its gene expression profiling studies, the team found it could distinguish "PFAPA flares from asymptomatic intervals, HPF [hereditary periodic fever] flares, and healthy controls." IL-1-related and IFN-induced genes are significantly overexpressed in patients experiencing the syndrome, the team reports. Further, the team successfully "treated five PFAPA patients with a recombinant IL-1 receptor antagonist," and therefore suggests that "IL-1 inhibition may ... be beneficial for treatment of PFAPA attacks."