Structural basis for iron piracy by pathogenic Neisseria

Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small-angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process.     

Evolutionary differentiation within the northern Great Basin pocket gopher, Thomomys townsendii I. Morphological variation

Geographic and nongeographic variation in morphology was examined in Thomomys townsendii . A univariate analysis of external and cranial characters from a large population sample (66 adults; fusion of cranial sutures used as aging criteria) was used to assess variation among three adult age classes and between sexes. Only minor variation is apparent among age classes; however, sexual dimorphism is pronounced. Univariate and multivariate techniques were used to analyze external and cranial measurements and pelage characters for adults throughout the species range. These analyses show little to support the seven subspecific designations recognized by Davis (1937). The general pattern is one of homogeneity throughout the range of Thomomys townsendii . With the possible exception of T. t. nevadensis samples, current subspecies are not defined as morphological units. In fact, differentiation is found among populations within some subspecies. The most apparent pattern seen in these analyses is the divergence between the Humboldt River (including Honey Lake Valley samples) and Snake River systems. These results will be considered with those of a companion paper on the genetic variation in this species to more adequately assess the patterns of differentiation in Thomomys townsendii .     

Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-A secretion

Secondary damage following spinal cord injury leads to non-reversible lesions and hampering of the reparative process. The local production of pro-inflammatory cytokines such as TNF-α can exacerbate these events. Oligodendrocyte death also occurs, followed by progressive demyelination leading to significant tissue degeneration. Dental stem cells from human apical papilla (SCAP) can be easily obtained at the removal of an adult immature tooth. This offers a minimally invasive approach to re-use this tissue as a source of stem cells, as compared to biopsying neural tissue from a patient with a spinal cord injury. We assessed the potential of SCAP to exert neuroprotective effects by investigating two possible modes of action: modulation of neuro-inflammation and oligodendrocyte progenitor cell (OPC) differentiation. SCAP were co-cultured with LPS-activated microglia, LPS-activated rat spinal cord organotypic sections (SCOS), and LPS-activated co-cultures of SCOS and spinal cord adult OPC. We showed for the first time that SCAP can induce a reduction of TNF-α expression and secretion in inflamed spinal cord tissues and can stimulate OPC differentiation via activin-A secretion. This work underlines the potential therapeutic benefits of SCAP for spinal cord injury repair.