Determining drug resistance trends will optimize treatment and public health responses.

Olfactomedin 4 (OLFM4) is a glycoprotein that has been found to be up-regulated in inflammatory bowel diseases and Helicobacter pylori infected patients. However, its role in biological processes such as inflammation or other immune response is not known. In this study, we generated OLFM4 KO mice to investigate potential role(s) of OLFM4 in gastric mucosal responses to H. pylori infection. H. pylori colonization in the gastric mucosa of OLFM4 KO mice was significantly lower compared with WT littermates. The reduced bacterial load was associated with enhanced infiltration of inflammatory cells in gastric mucosa. Production and expression of proinflammatory cytokines/chemokines such as IL-1β, IL-5, IL-12 p70, and MIP-1α was increased in OLFM4 KO mice compared with infected controls. Furthermore, we found that OLFM4 is a target gene of NF-κB pathway and has a negative feedback effect on NF-κB activation induced by H. pylori infection through a direct association with nucleotide oligomerization domain-1 (NOD1) and -2 (NOD2). Together these observations indicate that OLFM4 exerts considerable influence on the host defense against H. pylori infection acting through NOD1 and NOD2 mediated NF-κB activation and subsequent cytokines and chemokines production, which in turn inhibit host immune response and contribute to persistence of H. pylori colonization.NF-κB | nucleotide oligomerization domain-1 and -2

Although calmodulin (CaM) is known to play multiple regulatory roles in eukaryotes, its direct function as transcriptional regulator is unknown. Furthermore, the physiological functions of CaM are largely unknown in plants. Here, we show that one of the four Arabidopsis thaliana CaM isoforms, CAM7, is a transcriptional regulator that directly interacts with the promoters of light-inducible genes and promotes photomorphogenesis. CAM7 overexpression causes hyperphotomorphogenic growth and an increase in the expression of light-inducible genes. Mutations in CAM7 produce no visible effects on photomorphogenic growth, indicating likely redundant gene functions. However, cam7 mutants display reduced expression of light-inducible genes, and cam7 hy5 double mutants show an enhancement of the hy5 phenotype. Moreover, overexpression of CAM7 can partly suppress the hy5 phenotype, indicating that the two factors work together to control lightinduced seedling development. The mutational and transgenic studies, together with physiological analyses, illustrate the concerted function of CAM7 and HY5 basic leucine zipper transcription factor in Arabidopsis seedling development.

Background: Light is an important factor for plant growth and development. Results: GBF1 interacts with two other bZIP proteins, HY5 and HYH, in light signaling. Conclusion: This work demonstrates the functional interconnections of GBF1, HY5, and HYH. Significance: The knowledge gained in this study will help to understand light-controlled plant growth and development.

R ecently developed genomic editing technologies have the potential to be powerful tools for gene therapy because of their ability to inactivate genes, correct mutated sequences, or insert intact genes. While the genomic editing field is advancing at an exceptionally rapid pace, there remain key issues regarding development of appropriate preclinical assays to evalu-ate off-target effects and establish safety. In order to begin a dialogue on these issues, the National Institutes of Health (NIH) Office of Science Policy, in collaboration with several NIH-funded investigators and the NIH Recombinant DNA Advisory Committee, organized a workshop on 10 June 2014, in Bethesda, Maryland, to provide a forum to educate the scientific and oversight communities and the public on different genome editing technologies, clinical experiences to date, and the preclinical assays being developed to examine the precision of these tools and their suitability for clinical application.Targeted genome modification by designer nucleases is an emerging technology that can be used to investigate gene function and could also be used to treat genetic or acquired diseases. A wide range of genome alterations has been achieved by these nucleases, including localized mutagenesis, local and dispersed sequence replacements, large and small insertions and deletions, and even chromosomal translocations. The nuclease approach to targeted genome editing has been applied successfully to more than 50 different organisms, including crop plants, livestock, and humans. 1 Recently developed genome editing technologies such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases, and clustered regularly interspaced short