Published in Cancer cell
MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostat...
Published in Proceedings of the National Academy of Sciences of the United States of America
The suprachiasmatic nucleus (SCN) defines 24 h of time via a transcriptional/posttranslational feedback loop in which transactivation of Per (period) and Cry (cryptochrome) genes by BMAL1-CLOCK complexes is suppressed by PER-CRY complexes. The molecular/structural basis of how circadian protein complexes function is poorly understood. We describe a...
Published in PLoS computational biology
We present a novel regularization scheme called The Generalized Elastic Net (GELnet) that incorporates gene pathway information into feature selection. The proposed formulation is applicable to a wide variety of problems in which the interpretation of predictive features using known molecular interactions is desired. The method naturally steers sol...
Published in Environmental microbiology
Helicobacter pylori is a human-specific pathogen that chronically infects about 50% of the world's population. After travelling through the harsh environment of the stomach lumen, H. pylori colonizes the mucosal surface and within the glands of the human stomach. During colonization, H. pylori uses motility and its chemotaxis signalling system to s...
Published in Vaccine
The introduction of serogroup A meningococcal conjugate vaccine in the African meningitis belt required strengthened surveillance to assess long-term vaccine impact. The costs of implementing this strengthening had not been assessed. The ingredients approach was used to retrospectively determine bacterial meningitis surveillance costs in Chad and N...
Published in PloS one
The pattern of epidemic meningococcal disease in the African meningitis belt may be influenced by the background level of population immunity but this has been measured infrequently. A standardised enzyme-linked immunosorbent assay (ELISA) for measuring meningococcal serogroup A IgG antibodies was established at five centres within the meningitis b...
Published in Vaccine
Since 2010, countries in the African meningitis belt have been introducing a new serogroup A meningococcal conjugate vaccine (MenAfriVac(®)) through mass campaigns. With the subsequent decline in meningitis due to Neisseria meningitidis serogroup A (NmA) and relative increase in meningitis due to other serogroups, mainly N. meningitidis serogroup W...
Published in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
An enhanced meningitis surveillance network was established across the meningitis belt of sub-Saharan Africa in 2003 to rapidly collect, disseminate, and use district weekly data on meningitis incidence. Following 10 years' experience with enhanced surveillance that included the introduction of a group A meningococcal conjugate vaccine, PsA-TT (Men...
Published in Stem cell reports
Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem...
Published in ACS chemical biology
Marine natural products are an important source of lead compounds against many pathogenic targets. Herein, we report the discovery of lobosamides A-C from a marine actinobacterium, Micromonospora sp., representing three new members of a small but growing family of bacterially produced polyene macrolactams. The lobosamides display growth inhibitory ...
