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In follicular lymphoma (FL), surface immunoglobulin (sIg) carries mandatory N-glycosylation sites in the variable regions, inserted during somatic hypermutation. These glycosylation sites are tumor-specific, indicating a critical function in FL. Added glycan unexpectedly terminates at high mannose (Mann) and confers capability for sIg-mediated interaction with local macrophage-expressed DC-SIGN lectin resulting in low-level activation of upstream B-cell receptor signaling responses. Here we show that despite being of low-level, DC-SIGN induces a similar downstream transcriptional response to anti-IgM in primary FL cells, characterized by activation of pathways associated with B-cell survival, proliferation and cell–cell communication. Lectin binding was also able to engage post-transcriptional receptor cross-talk pathways since, like anti-IgM, DC-SIGN down-modulated cell surface expression of CXCR4. Importantly, pre-exposure of a FL-derived cell line expressing sIgM-Mann or primary FL cells to DC-SIGN, which does not block anti-IgM binding, reversibly paralyzed the subsequent Ca 2+ response to anti-IgM. These novel findings indicate that modulation of sIg function occurs in FL via lectin binding to acquired mannoses. The B-cell receptor alternative engagement described here provides two advantages to lymphoma cells: (i) activation of signaling, which, albeit of low-level, is sufficient to trigger canonical lymphoma-promoting responses, and (ii) protection from exogenous antigen by paralyzing anti-IgM-induced signaling. Blockade of this alternative engagement could offer a new therapeutic strategy.

Second, constructing a new facility at Grayslake also will be less expensive than leasing space at the University Station as proposed by its developer. The cost of building the center at Grayslake (and a downtown satellite) is estimated at $22.8 million, $8.3 million less than the Lakehurst proposal. Also, with a lease, the state still would not own the facility. The board's decision to place the University Center in Grayslake hinged on three factors: the need for an educational environment to help nurture its development; impending demographic shifts pushing the population to the west, north and central regions of Lake County; and the significant cost savings that new construction at Grayslake held over the lease arrangement proposed at Lakehurst. Many residents and officials have pointed out that the Lakehurst site is more accessible than Grayslake, particularly during rush hour. No one can deny that traffic is a critical problem, but it is pervasive in Lake County, not just in the Grayslake area. If anything, the debate over the University Center's location has sensitized more people to the issue and will likely provoke efforts to deal with it more quickly than might otherwise have happened. The widening of the intersection of highways 120 and 45 is under way, and Department of Transportation road plans for 2000 to 2004 include other projects aimed at relieving the congestion around CLC. The Board of Higher Education has written to the department urging it to give those projects high priority.

SPRINGFIELD-- A May 10 Tribune editorial encourages members of the Illinois legislature and the U.S. Congress to resist \"the political temptation to dictate employee benefits.\"

SPRINGFIELD-- A May 10 Tribune editorial encourages members of the Illinois legislature and the U.S. Congress to resist \"the political temptation to dictate employee benefits.\"

It seems that immediately following each Chicago and statewide election, Monday-morning quarterbacks emerge with the way \"it should have been done.\" After the furor dies down, though, the media and public turn their sights to other events.

A May 10 Tribune editorial encourages members of the Illinois legislature and the U.S. Congress to resist \"the political temptation to dictate employee benefits.\" And yet, when it comes to workers meeting their own family responsibilities to those same children, parents or spouses, the door is shut on a Family Leave and Responsibility Policy that permits workers a modest (eight weeks in the Illinois law) unpaid leave to meet family needs.

Illinois faces a crisis when it comes to helping low-income families protect their legal rights. There are only the equivalent of 280 full-time legal-aid lawyers in the entire state--a ratio of one legal-aid lawyer for every 4,752 legal problems faced by the poor. Out of the 10 most populous states, Illinois ranks last, spending less than $500,000 annually for civil legal aid, versus the national average of $6.8 million. These figures are simply unacceptable.

Agricultural biotechnology is limited by the inefficiencies of conventional random mutagenesis and transgenesis. Because targeted genome modification in plants has been intractable, plant trait engineering remains a laborious, time-consuming and unpredictable undertaking. Here we report a broadly applicable, versatile solution to this problem: the use of designed zinc-finger nucleases (ZFNs) that induce a double-stranded break at their target locus. We describe the use of ZFNs to modify endogenous loci in plants of the crop species Zea mays. We show that simultaneous expression of ZFNs and delivery of a simple heterologous donor molecule leads to precise targeted addition of an herbicide-tolerance gene at the intended locus in a significant number of isolated events. ZFN-modified maize plants faithfully transmit these genetic changes to the next generation. Insertional disruption of one target locus, IPK1, results in both herbicide tolerance and the expected alteration of the inositol phosphate profile in developing seeds. ZFNs can be used in any plant species amenable to DNA delivery; our results therefore establish a new strategy for plant genetic manipulation in basic science and agricultural applications.

Efficient incorporation of novel DNA sequences into a specific site in the genome of living human cells remains a challenge despite its potential utility to genetic medicine, biotechnology, and basic research. We find that a precisely placed double-strand break induced by engineered zinc finger nucleases (ZFNs) can stimulate integration of long DNA stretches into a predetermined genomic location, resulting in high-efficiency site-specific gene addition. Using an extrachromosomal DNA donor carrying a 12-bp tag, a 900-bp ORF, or a 1.5-kb promoter-transcription unit flanked by locus-specific homology arms, we find targeted integration frequencies of 15%, 6%, and 5%, respectively, within 72 h of treatment, and with no selection for the desired event. Importantly, we find that the integration event occurs in a homology-directed manner and leads to the accurate reconstruction of the donor-specified genotype at the endogenous chromosomal locus, and hence presumably results from synthesis-dependent strand annealing repair of the break using the donor DNA as a template. This site-specific gene addition occurs with no measurable increase in the rate of random integration. Remarkably, we also find that ZFNs can drive the addition of an 8-kb sequence carrying three distinct promoter-transcription units into an endogenous locus at a frequency of 6%, also in the absence of any selection. These data reveal the surprising versatility of the specialized polymerase machinery involved in double-strand break repair, illuminate a powerful approach to mammalian cell engineering, and open the possibility of ZFN-driven gene addition therapy for human genetic disease.