32 research outputs found
Transcriptome Analysis of Neisseria meningitidis in Human Whole Blood and Mutagenesis Studies Identify Virulence Factors Involved in Blood Survival
During infection Neisseria meningitidis (Nm) encounters multiple
environments within the host, which makes rapid adaptation a crucial factor for
meningococcal survival. Despite the importance of invasion into the bloodstream
in the meningococcal disease process, little is known about how Nm adapts to
permit survival and growth in blood. To address this, we performed a time-course
transcriptome analysis using an ex vivo model of human whole
blood infection. We observed that Nm alters the expression of â30% of
ORFs of the genome and major dynamic changes were observed in the expression of
transcriptional regulators, transport and binding proteins, energy metabolism,
and surface-exposed virulence factors. In particular, we found that the gene
encoding the regulator Fur, as well as all genes encoding iron uptake systems,
were significantly up-regulated. Analysis of regulated genes encoding for
surface-exposed proteins involved in Nm pathogenesis allowed us to better
understand mechanisms used to circumvent host defenses. During blood infection,
Nm activates genes encoding for the factor H binding proteins, fHbp and NspA,
genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as
several less characterized surface-exposed proteins that might have a role in
blood survival. Through mutagenesis studies of a subset of up-regulated genes we
were able to identify new proteins important for survival in human blood and
also to identify additional roles of previously known virulence factors in
aiding survival in blood. Nm mutant strains lacking the genes encoding the
hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and
NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate
permease LctP were sensitive to killing by human blood. This increased knowledge
of how Nm responds to adaptation in blood could also be helpful to develop
diagnostic and therapeutic strategies to control the devastating disease cause
by this microorganism
Effect of Age on Variability in the Production of Text-Based Global Inferences
As we age, our differences in cognitive skills become more visible, an effect especially true for memory and problem solving skills (i.e., fluid intelligence). However, by contrast with fluid intelligence, few studies have examined variability in measures that rely on oneâs world knowledge (i.e., crystallized intelligence). The current study investigated whether age increased the variability in text based global inference generationâa measure of crystallized intelligence. Global inference generation requires the integration of textual information and world knowledge and can be expressed as a gist or lesson. Variability in generating two global inferences for a single text was examined in young-old (62 to 69 years), middle-old (70 to 76 years) and old-old (77 to 94 years) adults. The older two groups showed greater variability, with the middle elderly group being most variable. These findings suggest that variability may be a characteristic of both fluid and crystallized intelligence in aging