Hydrologic Analysis of Two Headwater Lake Basins of Differing Lake pH in the West-central Adirondack Mountains of New York

Hydrologic analysis of two headwater lake basins in the Adirondack Mountains, New York, during 1980-81 indicates that the degree of neutralization of acid precipitation is controlled by the groundwater contribution to the lake. According to flow-duration analyses, daily mean outflow/unit area from the neutral lake (Panther Lake, pH 5-7) was more sustained and contained a higher percentage of groundwater than that of the acidic lake (Woods Lake, pH 4-5). Outflow recession rates and maximum base-flow rates, derived from individual recession curves, were 3.9 times and 1.5 times greater, respectively, in the neutral-lake basin than in the acidic-lake basin. Groundwater contribution to lake outflow was also calculated from a lake-water budget; the groundwater contribution to the neutral lake was about 10 times greater than that to the acidic lake. Thick sandy till forms the groundwater reservoir and the major recharge area in both basins but covers 8.5 times more area in the neutral-lake basin than in the acidic-lake basin. More groundwater storage within the neutral basin provides longer contact time with neutralizing minerals and more groundwater discharge. As a result, the neutral lake has relatively high pH and alkalinity, and more net cation transport. (USGS

Phosphofructokinase 1 Glycosylation Regulates Cell Growth and Metabolism

Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention

Activation of the Transcriptional Function of the NF-κB Protein c-Rel by O-GlcNAc Glycosylation

The transcription factor nuclear factor κB (NF-κB) rapidly reprograms gene expression in response to various stimuli, and its activity is regulated by several posttranslational modifications, including phosphorylation, methylation, and acetylation. The addition of O-linked b-N-acetylglucosamine (a process known as O-GlcNAcylation) is an abundant posttranslational modification that is enhanced in conditions such as hyperglycemia and cellular stress. We report that the NF-κB subunit c-Rel is modified and activated by O-GlcNAcylation. We identified serine 350 as the site of O-GlcNAcylation, which was required for the DNA binding and transactivation functions of c-Rel. Blocking the O-GlcNAcylation of this residue abrogated c-Rel–mediated expression of the cytokine-encoding genes IL2, IFNG, and CSF2 in response to T cell receptor (TCR) activation, whereas increasing the extent of O-GlcNAcylation of cellular proteins enhanced the expression of these genes. TCR- or tumor necrosis factor (TNF)–induced expression of other NF-κB target genes, such as NFKBIA (which encodes IkBa) and TNFAIP3 (which encodes A20), occurred independently of the O-GlcNAcylation of c-Rel. Our findings suggest a stimulus-specific role for hyperglycemia-induced O-GlcNAcylation of c-Rel in promoting T cell–mediated autoimmunity in conditions such as type 1 diabetes by enhancing the production of T helper cell cytokines

Agri-Environmental Policy at the Crossroads: Guideposts on a Changing Landscape

Agri-environmental policy is at a crossroads. Over the past 20 years, a wide range of policies addressing the environmental implications of agricultural production have been implemented at the Federal level. Those policies have played an important role in reducing soil erosion, protecting and restoring wetlands, and creating wildlife habitat. However, emerging agri-environmental issues, evolution of farm income support policies, and limits imposed by trade agreements may point toward a rethinking of agri-environmental policy. This report identifies the types of policy tools available and the design features that have improved the effectiveness of current programs. It provides an indepth analysis of one policy tool that may be an important component of a future policy package-agri-environmental payments. The analysis focuses on issues and tradeoffs that policymakers would face in designing a program of agri-environmental payments.conservation programs, environmental policy, agricultural policy, policy instruments, agricultural program design, soil erosion, nitrogen runoff, Environmental Economics and Policy,

Relativity tests by complementary rotating Michelson-Morley experiments

We report Relativity tests based on data from two simultaneous Michelson-Morley experiments, spanning a period of more than one year. Both were actively rotated on turntables. One (in Berlin, Germany) uses optical Fabry-Perot resonators made of fused silica; the other (in Perth, Australia) uses microwave whispering-gallery sapphire resonators. Within the standard model extension, we obtain simultaneous limits on Lorentz violation for electrons (5 coefficients) and photons (8) at levels down to $10^{-16}$, improved by factors between 3 and 50 compared to previous work.Comment: 5 pages revtex, 2 figure

The Fluctuating Phenotype of the Lymphohematopoietic Stem Cell with Cell Cycle Transit

The most primitive engrafting hematopoietic stem cell has been assumed to have a fixed phenotype, with changes in engraftment and renewal potential occurring in a stepwise irreversible fashion linked with differentiation. Recent work shows that in vitro cytokine stimulation of murine marrow cells induces cell cycle transit of primitive stem cells, taking 40 h for progression from G0 to mitosis and 12 h for subsequent doublings. At 48 h of culture, progenitors are expanded, but stem cell engraftment is markedly diminished. We have investigated whether this effect on engraftment was an irreversible step or a reversible plastic feature correlated with cell cycle progression. Long-term engraftment (2 and 6 mo) of male BALB/c marrow cells exposed in vitro to interleukin (IL)-3, IL-6, IL-11, and steel factor was assessed at 2–4-h intervals of culture over 24–48 h using irradiated female hosts; the engraftment phenotype showed marked fluctuations over 2–4-h intervals, with engraftment nadirs occurring in late S and early G2. These data show that early stem cell regulation is cell cycle based, and have critical implications for strategies for stem cell expansion and engraftment or gene therapy, since position in cell cycle will determine whether effective engraftment occurs in either setting

Cytokine-facilitated transduction leads to low-level engraftment in nonablated hosts

Using a murine bone marrow transplantation model, we evaluated the long-term engraftment of retrovirally transduced bone marrow cells in nonmyeloablated hosts. Male bone marrow was stimulated in a cocktail of interleukin-3 (IL-3), IL-6, IL-11, and stem cell factor (SCF) for 48 hours, then cocultured on the retroviral producer line MDR18.1 for an additional 24 hours. Functional transduction of hematopoietic progenitors was detected in vitro by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of multiple drug resistance 1 (MDR1) mRNA from high proliferative potential-colony forming cell (HPP-CFC) colonies. After retroviral transduction, male bone marrow cells were injected into nonablated female mice. Transplant recipients received three TAXOL (Bristol-Myers, Princeton, NJ) injections (10 mg/kg) over a 14-month period. Transplant recipient tissues were analyzed by Southern blot and fluorescence in situ hybridization for Y-chromosome-specific sequences and showed donor cell engraftment of approximately 9%. However, polymerase chain reaction amplification of DNAs from bone marrow, spleen, and peripheral blood showed no evidence of the transduced MDR1 gene. RT-PCR analysis of total bone marrow RNA showed that transcripts from the MDR1 gene were present in a fraction of the engrafted donor cells. These data show functional transfer of the MDR1 gene into nonmyeloablated murine hosts. However, the high rates of in vitro transduction into HPP-CFC, coupled with the low in vivo engraftment rate of donor cells containing the MDR1 gene, suggest that the majority of stem cells that incorporated the retroviral construct did not stably engraft in the host. Based on additional studies that indicate that ex vivo culture of bone marrow induces an engraftment defect concomitantly with progression of cells through S phase, we propose that the cell cycle transit required for proviral integration reduces or impairs the ability of transduced cells to stably engraft