Structural modeling and functional analysis of the essential ribosomal processing protease Prp from Staphylococcus aureus

In Firmicutes and related bacteria, ribosomal large subunit protein L27 is encoded with a conserved N-terminal extension that is removed to expose residues critical for ribosome function. Bacteria encoding L27 with this N-terminal extension also encode a sequence-specific cysteine protease, Prp, which carries out this cleavage. In this work, we demonstrate that L27 variants with an un-cleavable N-terminal extension, or lacking the extension (pre-cleaved), are unable to complement an L27 deletion in Staphylococcus aureus. This indicates that N-terminal processing of L27 is not only essential but possibly has a regulatory role. Prp represents a new clade of previously uncharacterized cysteine proteases, and the dependence of S. aureus on L27 cleavage by Prp validates the enzyme as a target for potential antibiotic development. To better understand the mechanism of Prp activity, we analyzed Prp enzyme kinetics and substrate preference using a fluorogenic peptide cleavage assay. Molecular modeling and site-directed mutagenesis implicate several residues around the active site in catalysis and substrate binding, and support a structural model in which rearrangement of a flexible loop upon binding of the correct peptide substrate is required for the active site to assume the proper conformation. These findings lay the foundation for the development of antimicrobials that target this novel, essential pathway

Aquifer Depletion and the Cost of Water Conservation: The Southern High Plains of Texas Case

Irrigated agriculture has played a vital role in the development and growth of the Great Plains Region of the United States. The primary source of water for irrigation in this region is the Ogallala Aquifer. The Southern portion of the Ogallala Aquifer is considered exhaustible due to the low level of recharge relative to the quantities of water pumped. Analysis and evaluation of water conservation policies which could extend the economic life of the Ogallala Aquifer in the Southern High Plains of Texas and Eastern New Mexico, and which could contribute to maintaining the viability of the regional economy is important. This study evaluates the impacts of water conservation policies which limit drawdown of the Ogallala Aquifer. County level dynamic optimization models maximizing net present value of net returns to land, management, groundwater, and irrigation systems over a sixty year planning horizon were formulated to evaluate three aquifer drawdown restrictions. The results of this study indicate that because of the differences in hydrologic characteristics and current irrigation levels across counties in the study area, blanket water conservation policies for the region as a whole are likely to be inefficient. This study concludes that for this region, water conservation policies that focus on counties that would deplete the aquifer to less than 30 ft. of saturated thickness possess the lowest implicit cost of conserving saturated thickness.water conservation, water policy evaluation, aquifer management, dynamic optimization, Resource /Energy Economics and Policy,

Policy Alternatives for the Southern Ogallala Aquifer

Due to declining water levels in the Ogallala Aquifer, policy alternatives for extending the life of the aquifer for irrigation and other purposes are evaluated. The study concludes that blanket water conservation policies for the region are likely to be inefficient because of economic and hydrologic differences in the region.Resource /Energy Economics and Policy,

Human Cloning

In December 2005, an investigation by Seoul National University, South Korea, found that scientist Hwang Woo Suk had fabricated results on deriving patientmatched stem cells from cloned embryos — a major setback for the field. In May 2005 Hwang had announced a significant advance in creating human embryos using cloning methods and in isolating human stem cells from cloned embryos. These developments have contributed to the debate in the 109th Congress on the moral and ethical implications of human cloning. Scientists in other labs, including Harvard University and the University of California at San Francisco, intend to produce cloned human embryos in order to derive stem cells for medical research on diabetes, Parkinson’s disease, and other diseases. President Bush announced in August 2001 that for the first time federal funds would be used to support research on human embryonic stem cells, but funding would be limited to “existing stem cell lines.” Federal funds can not be used for the cloning of human embryos for any purpose, including stem cell research. In July 2002 the President’s Council on Bioethics released its report on human cloning which unanimously recommended a ban on reproductive cloning and, by a vote of 10 to 7, a four-year moratorium on cloning for medical research purposes. The ethical issues surrounding reproductive cloning (commodification, safety, identity ), and therapeutic cloning (embryos’ moral status, relief of suffering), impact various proposals for regulation, restrictions, bans, and uses of federal funding. In January 2002, the National Academies released Scientific and Medical Aspects of Human Reproductive Cloning. It recommended that the U.S. ban human reproductive cloning aimed at creating a child. It suggested the ban be enforceable and carry substantial penalties. The panel noted that the ban should be reconsidered within five years. However, the panel concluded that cloning to produce stem cells should be permitted because of the potential for developing new therapies and advancing biomedical knowledge. On May 24, 2005, the House passed H.R. 810 (Castle), which would allow federal support of research that uses human embryonic stem cells regardless of the date on which the stem cells were derived from a human embryo, thus negating the Bush stem cell policy limitation on “existing stem cell lines.” In July of 2006, the Senate passed H.R. 810 and President Bush vetoed it, the first veto of his presidency. An attempt in the House to override the veto was unsuccessful. Action on the Weldon bill (which passed the House in the 108th Congress and stalled in the Senate) is also possible; it was reintroduced in the 109th Congress as H.R. 1357 and S. 658 (Brownback). The bill bans the process of cloning as well as the importation of any product derived from an embryo created via cloning. It bans not only reproductive applications, but also research on therapeutic uses, which has implications for stem cell research. Advocates of the legislative ban say that allowing any form of human cloning research to proceed raises serious ethical issues and will inevitably lead to the birth of a baby that is a human clone. Critics of the ban argue that the measure would curtail medical research and prevent Americans from receiving life-saving treatments created overseas. This report will be updated as needed

Stem Cell Research: Federal Research Funding and Oversight

Embryonic stem cells have the ability to develop into virtually any cell in the body, and they may have the potential to treat medical conditions such as diabetes and Parkinson’s disease. In August 2001, President Bush announced that for the first time, federal funds would be used to support research on human embryonic stem cells, but funding would be limited to “existing stem cell lines.” NIH has established a registry of 78 human embryonic stem cell lines that are eligible for use in federally funded research, but only 21 cell lines are currently available. Scientists are concerned about the quality and longevity of these 21 stem cell lines. NIH Director Elias Zerhouni stated before a Senate subcommittee in March 2007 that research advancement requires access to new human embryonic stem cell lines. Some have argued that adult stem cells (from bone marrow or umbilical cord blood) should be pursued instead of embryonic stem cells because they believe the derivation of stem cells from embryos is ethically unacceptable. The NIH Director and many other scientists believe adult stem cells should not be the sole target of research because of important scientific and technical limitations. Reports issued by NIH and the Institute of Medicine state that both embryonic and adult stem cell research should be pursued. Some scientists are exploring the possibility of obtaining human embryonic stem cells that bypass the destruction of living human embryos. The President’s Council on Bioethics cited four potential alternative sources of human embryonic stem cells in a May 2005 paper. A number of pro-life advocates support stem cell research; those opposed are concerned that stem cell isolation requires embryo destruction. On January 11, 2007, the House passed H.R. 3 (DeGette) on a vote of 253 to 174. H.R. 3 would allow federal support of research that utilizes human embryonic stem cells regardless of the date on which the stem cells were derived from a human embryo, and thus negate the August 2001 Bush stem cell policy limitation. On April 11, 2007, the Senate passed S. 5 (Reid), which has the same text as H.R. 3 and an additional section supporting research on alternative human pluripotent stem cells. The Senate also passed S. 30 (Coleman) on April 11, 2007. Unlike H.R. 3 and S. 5, S. 30 provides support only for research on alternative human pluripotent stem cells. (The 109th Congress passed legislation identical to H.R. 3, H.R. 810 (Castle), but President Bush vetoed it, the first veto of his presidency. An attempt in the House to override the veto was unsuccessful.) On the related issue of human cloning, S. 812 (Hatch) would ban human reproductive cloning but allow for the therapeutic uses of the technique provided that a number of ethical requirements are observed. In contrast, the Weldon bill (which passed the House in the 107th and 108th Congresses) and S. 1036 (Brownback) would ban not only reproductive applications, but also research on therapeutic uses, which has implications for stem cell research. Advocates of the legislative ban say that allowing any form of human cloning research to proceed raises serious ethical issues, and will inevitably lead to the birth of a baby who is a human clone. Critics argue that the measure would curtail medical research and prevent Americans from receiving life-saving treatments created overseas. This report will be updated as needed

Economic Efficiency of Short-Term Versus Long-Term Water Rights Buyouts

Because of the decline of the Ogallala Aquifer, water districts, regional water managers, and state water officers are becoming increasingly interested in conservation policies. This study evaluates both short-term and long-term water rights buyout policies. This research develops dynamic production functions for the major crops in the Texas Panhandle. The production functions are incorporated into optimal temporal allocation models that project annual producer behavior, crop choices, water use, and aquifer declines over 60 years. Results suggest that long-term buyouts may be more economically efficient than short-term buyouts.dynamic production function, nonlinear optimization, Ogallala Aquifer, water rights buyout, Agribusiness, Environmental Economics and Policy, Q30, Q32, Q38,

Oscillations in meta-generalized-gradient approximation potential energy surfaces for dispersion-bound complexes

© 2009 American Institute of Physics. The electronic version of this article is the complete one and can be found at: http://dx.doi.org/10.1063/1.3177061DOI: 10.1063/1.3177061Meta-generalized-gradient approximations (meta-GGAs) in density-functional theory are exchange-correlation functionals whose integrands depend on local density, density gradient, and also the kinetic-energy density. It has been pointed out by Johnson et al. [Chem. Phys. Lett. 394, 334 (2004) ] that meta-GGA potential energy curves in dispersion-bound complexes are susceptible to spurious oscillations unless very large integration grids are used. This grid sensitivity originates from the saddle-point region of the density near the intermonomer midpoint. Various dimensionless ratios involving the kinetic-energy density, found in typical meta-GGAs, may be ill-behaved in this region. Grid sensitivity thus arises if the midpoint region is sampled by too sparse a grid. For most meta-GGAs, standard grids do not suffice. Care must be taken to avoid this problem when using, or constructing, meta-GGAs

Stem Cell Research

Embryonic stem cells have the ability to develop into virtually any cell in the body and they may have the potential to treat medical conditions such as diabetes and Parkinson’s disease. In August 2001, President Bush announced that for the first time federal funds would be used to support research on human embryonic stem cells, but funding would be limited to “existing stem cell lines.

Human Cloning

This report provides information about the Human Cloning where a human embryo produced via cloning involves the process called somatic cell nuclear transfer. The nuclear of the egg is removed and replaced with a mature body cell

Stem Cell Research

Embryonic stem cells have the ability to develop into virtually any cell in the body, and they may have the potential to treat medical conditions such as diabetes and Parkinson’s disease. In August 2001, President Bush announced that for the first time federal funds would be used to support research on human embryonic stem cells, but funding would be limited to “existing stem cell lines.” The National Institutes of Health (NIH) has established the Human Embryonic Stem Cell Registry, which lists 78 stem cell lines that are eligible for use in federally funded research. However, only 22 embryonic stem cell lines are currently available. Scientists are concerned about the quality, and longevity of these stem cell lines