X-linked neutropenia (XLN) is caused by activating mutations in the Wiskott-Aldrich syndrome protein (WASP) that result in aberrant autoinhibition. Although patients with XLN appear to have only defects in myeloid lineages, we hypothesized that activating mutations of WASP are likely to affect the immune system more broadly. We generated mouse models to assess the role of activating WASP mutations associated with XLN (XLN-WASP) in lymphocytes. XLN-WASP is expressed stably in B and T cells and induces a marked increase in polymerized actin. XLN-WASP–expressing B and T cells migrate toward chemokines but fail to adhere normally. In marked contrast to WASP-deficient cells, XLN-WASP–expressing T cells proliferate normally in response to cell-surface receptor activation. However, XLN-WASP–expressing B cells fail to proliferate and secrete lower amounts of antibodies. Moreover, XLN-WASP expression in lymphocytes results in modestly increased apoptosis associated with increased genomic instability. These data indicate that there are unique requirements for the presence and activation status of WASP in B and T cells and that WASP-activating mutations interfere with lymphocyte cell survival and genomic stability.
A procedure to eliminate Escherichia coli in dairy cattle
manure was developed. E. coli persisted in fresh manure and
farm storage tanks, and viable counts ranged from 105
to 108/g. If the feces to urine ratio of fresh manure was
decreased from 2.2 to 1, E. coli did not persist for ≥10 days
(<10 viable cells/g), and it appeared that the urine was
killing E. coli. Fecal urease contamination produced CO2, and
16% was trapped as carbonate. When urine pH was
decreased, antimicrobial effect was lost, even if the pH
was readjusted to 8.5. When E. coli K-12 and O157:H7 were
treated with Na2CO3 (100 mM, pH 8.5, 24 h), viable cells
were not detected. The E. coli count of manure (feces to
urine ratio of 2.2:1) was decreased by Na2CO3 addition (8
g/kg), but pH sometimes declined and carbonate was
lost. When NaOH was included (2 g/kg), Na2CO3 additions
could be decreased (4 g/kg), and treatment time was 5
days. Treatment cost could be <$10 year-1 (dairy cow)-1.
Water dilution (3-fold) did not diminish the effectiveness
of the carbonate/alkali treatment, and viability was <10 cells/g.
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