The goal of this experiment was to examine the innate immune response to helminth infection in the lung. Hookworms (like many other helminths) use an obligate migration pathway through the lung. Their infection has been characterized in the gut in detail, but early immune responses in the lung have not been fully characterized.
Innate immune responses to lung-stage helminth infection induce alternatively activated alveolar macrophages.
No sample metadata fields
View SamplesUbiquitin and ubiquitin-like proteins (UBLs) are directed to targets by cascades of E1, E2, and E3 enzymes. The largest ubiquitin E3 subclass consists of cullin-RING ligases (CRLs), which contain one each of several cullins (CUL1, -2, -3, -4, or -5) and RING proteins (RBX1 or -2). CRLs are activated by ligation of the UBL NEDD8 to a conserved cullin lysine. How is cullin NEDD8ylation specificity established? Here we report that, like UBE2M (also known as UBC12), the previously uncharacterized E2 UBE2F is a NEDD8-conjugating enzyme in vitro and in vivo. Biochemical and structural analyses indicate how plasticity of hydrophobic E1-E2 interactions and E1 conformational flexibility allow one E1 to charge multiple E2s. The E2s have distinct functions, with UBE2M/RBX1 and UBE2F/RBX2 displaying different target cullin specificities. Together, these studies reveal the molecular basis for and functional importance of hierarchical expansion of the NEDD8 conjugation system in establishing selective CRL activation.
E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification.
No sample metadata fields
View SamplesDown syndrome is the most common form of genetic mental retardation. How Trisomy 21 causes mental retardation remains unclear and its effects on adult neurogenesis have not been addressed. To gain insight into the mechanisms causing mental retardation we used microarrays to investigate gene expression differences between Ts1Cje (a mouse model of Down syndrome) and C57BL/6 littermate control neurospheres. The neurospheres were generated from neural stem cells and progenitors isolated from the lateral walls of the lateral ventricles from adult mice.
Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome.
Sex, Disease
View SamplesThis study was undertaken in order to characterize the functions of Rex-1 and identify potential Rex-1 target genes.Both alleles of the Rex-1 gene were disrupted in J1 mouse embryonic stem cells. Gene expression levels in one of the resulting Rex-1 knockout cell lines was compared to that of J1 wild type cells.
Analysis of Rex1 (zfp42) function in embryonic stem cell differentiation.
No sample metadata fields
View SamplesAlthough it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that factors on chromosomes (chr) 8, 11, and 18 are responsible for susceptibility to S. aureus sepsis in A/J mice. F1 mice from C57BL/6J X CSS8 cross (C8A) and C57BL/6J X CSS18 (C18A) were also susceptible to S. aureus (median survival < 48 h), whereas F1 mice from C57BL/6J X CSS11 cross (C11A) were resistant (median survival > 120 h) to S. aureus. Bacterial loads in the kidney were consistent with F1 median survivals, with higher bacterial counts in susceptible mice. No sexlinked associations with susceptibility were noted in F1 intercrosses. Using whole genome transcription profiling, we identified a total of 192 genes on chromosomes 8, 11, and 18 which are differentially expressed between A/J and C57BL/6J in the setting of S. aureus infection. Of these, 28 genes had Gene Ontology annotations indicating a potential immune response function. These 28 genes are associated with susceptibility to S. aureus in A/J mice, and are potential determinants of susceptibility to S. aureus infection in humans.
Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses.
Time
View SamplesWe used microarrays to detail the global gene expression and identified differentially expressed gene list between wild-type anterior prostates and Ptenpc-/- anterior prostates, Ptenpc-/-Smad4pc-/- and Ptenpc-/- anterior prostates, Ptenpc-/-p53pc-/- and Ptenpc-/- anterior prostates at 15 weeks of age.
SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression.
Age, Specimen part
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