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S Benkovic

Publications and source records attributed to S Benkovic.

8 recordsLinked to original sources
PubMed2001

To trade or not to trade? Criteria for applying cap and trade.

The use of emissions trading (cap and trade) is gaining worldwide recognition as an extremely effective policy tool. The U.S. Sulfur Dioxide (SO2) Emissions Trading Program has achieved an unprecedented level of environmental protection in a cost-effective manner. The successful results of the program have led domestic and foreign governments to consider the application of cap and trade to address other air quality issues. Certain analyses are particularly important in determining whether or not cap and trade is an appropriate policy tool. This paper offers a set of questions that can be used as criteria for determining whether or not cap and trade is the preferred policy approach to an environmental problem.

Acid Rain↗
PubMed2000

Long-term induction of Fos-related antigen-2 after methamphetamine-, methylenedioxymethamphetamine-, 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine- and trimethyltin-induced brain injury.

A long-term induction of Fos-related antigens has been shown in neurons after brain injury, suggesting that Fos-related antigens are involved in enhancing the transcription of genes related to the process of regeneration and repair. In the present study, we report that levels of Fos-related antigen-2 are elevated in several models of chemically induced brain injury. Trimethyltin, which causes degeneration of neurons primarily in the hippocampus and other limbic regions, results in a five-fold induction of Fos-related antigen-2 immunoreactivity in neurons in the pyramidal and dentate layers of the hippocampus starting at seven days post-treatment and persisting for 60days. Methamphetamine and methylenedioxymethamphetamine, agents which cause degeneration of dopaminergic nerve terminals in the striatum of the mouse, cause an increase in Fos-related antigen-2 immunoreactivity which begins at three days post-treatment and returns to basal levels by days 5 and 15, respectively. Treatment with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine elevated levels of Fos-related antigen-2 in the mouse striatum at three days post-treatment. This abbreviated time-course of Fos-related antigen-2 induction is consistent with less severe insult (terminal damage) relative to trimethyltin (cell death), but induction occurs during the period of regeneration and repair in both models. Dexfenfluramine, a non-neurotoxic amphetamine, does not induce Fos-related antigen-2 expression. Decreasing core temperature of the mouse, which blocks amphetamine-induced neurotoxicity, also blocks Fos-related antigen-2 induction. In summary, Fos-related antigen-2 is induced in models of both cell death and terminal degeneration, suggesting that this transcription factor may serve as a universal signal transduction molecule involved in the regulation of genes related to regeneration and repair in the CNS.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1999

Induction of presenilins in the rat brain after middle cerebral arterial occlusion.

In the present study, we have examined the expression of both presenilins in the rat hippocampus, cortex, striatum, and cerebellum after middle cerebral artery occlusion (MCA-O), an animal model of ischemia. The cortex showed the greatest increase in PS mRNA levels (7-10-fold) at 4 and 8 days posttreatment. Presenilin-1 (PS-1) levels in the contralateral cortex were significantly increased 1 day after MCA-O. In comparison, PS mRNA content was only modestly elevated in the hippocampus and striatum at 4 and 8 days after MCA-O (30-100% changes). Other Alzheimer's disease (AD)-related genes, amyloid precursor protein and apolipoprotein E, are induced in brain injury suggesting that these AD-related genes may well be components of a brain-injury response. Thus, a breakdown in this response via cerebrovascular disease and/or genetic mutation may contribute to AD pathology.

Alzheimer Disease↗
PubMed1998

Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes.

Genetic causes of Alzheimer's disease (AD) include mutations in the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) genes. The mutant APP(K670N,M671L) transgenic line, Tg2576, shows markedly elevated amyloid beta-protein (A beta) levels at an early age and, by 9-12 months, develops extracellular AD-type A beta deposits in the cortex and hippocampus. Mutant PS1 transgenic mice do not show abnormal pathology, but do display subtly elevated levels of the highly amyloidogenic 42- or 43-amino acid peptide A beta42(43). Here we demonstrate that the doubly transgenic progeny from a cross between line Tg2576 and a mutant PS1M146L transgenic line develop large numbers of fibrillar A beta deposits in cerebral cortex and hippocampus far earlier than their singly transgenic Tg2576 littermates. In the period preceding overt A beta deposition, the doubly transgenic mice show a selective 41% increase in A beta42(43) in their brains. Thus, the development of AD-like pathology is substantially enhanced when a PS1 mutation, which causes a modest increase in A beta42(43), is introduced into Tg2576-derived mice. Remarkably, both doubly and singly transgenic mice showed reduced spontaneous alternation performance in a "Y" maze before substantial A beta deposition was apparent. This suggests that some aspects of the behavioral phenotype in these mice may be related to an event that precedes plaque formation.

Alzheimer Disease↗
PubMed1994

Effect of a thiobenzimidazolone derivative on DNA strand transfer catalyzed by HIV-1 reverse transcriptase.

Thiobenzimidazolone (TIBO) derivatives are known inhibitors of the DNA polymerase activity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The effect of a TIBO derivative ((+)-S-4,5,6,7-tetrahydro-9-chloro-5- methyl-6-(3-methyl-2-butenyl)-imidazol[4,5,1-jk]1,4-benzodiazapine -2-thione ) on the DNA strand transfer reaction catalyzed by HIV-1 RT (which is a function of both the DNA polymerase and RNase H activities) was investigated by delineating the effect of the drug on the constitutive DNA polymerase and RNase H activities) was investigated by delineating the effect of the drug on the constitutive DNA polymerase and RNase H activities. Single nucleotide incorporation on template-primer 1 was used to study the DNA polymerase activity of HIV-1 RT while template-primer 2 was used to study the effect of TIBO on the RNase H activity (polymerase independent). The drug was found to decrease the amplitude of the presteady-state burst when preequilibrated with the enzyme-substrate complex besides decreasing the steady-state rate of single nucleotide incorporations. In the absence of preincubation, TIBO did not affect the burst amplitude but decreased the steady-state rate after the pre-transient phase. This suggested that binding of TIBO to RT was affected by the presence of template-primer and required dissociation of the enzyme from the template-primer for effective binding. The polymerase-independent RNase H activity was activated in the presence of TIBO. The effect of TIBO on the overall process of DNA strand transfer is a balance between its inhibition of the polymerase activity and its activation of the RNase H activity.

Antiviral Agents↗
PubMed1994

Catalytic antibodies: perusing combinatorial libraries.

Combinatorial libraries are a promising alternative for isolating catalytic antibodies produced by the immune system in response to the transition-state analog of a given reaction. Large, diverse panels of antibodies with high affinity for the transition-state analog can be isolated using screening or selection approaches. Furthermore, we have estimated that nucleotide sequences that bear close similarity to the sequence for a known catalytic antibody occur in combination at frequencies sufficient for their detection in such libraries.

Amino Acid Sequence↗
PubMed1991

Localization of insulin-like growth factor-1 mRNA in murine central nervous system during postnatal development.

Insulin-like growth factor-1 (IGF-1) is believed to play a role in the regulation of brain growth. The identity of cells responsible for its synthesis in the immature brain, however, has not been established. To identify potential sites of IGF-1 synthesis, in situ hybridization has been utilized to localize IGF-1 mRNA in the murine brain during the first postnatal month. Although IGF-1 mRNA was detected in all regions of the neonatal brain, there was considerable regional variation in the level of expression. Neurons were the principle sites IGF-1 mRNA expression and expression was typically restricted to one or two neuronal cell types within each region. In the cerebellar cortex, for example, only Purkinje cells hybridized to the IGF-1 probe. In contrast to gray matter, IGF-1 labeled cells were rarely found in presumptive white matter tracts of the forebrain. The hybridization signal was most prominent in regions where neurogenesis persisted after birth, including the cerebellum, olfactory bulb, and hippocampal complex. The timing of IGF-1 mRNA expression appeared to be temporally related to local neuronal proliferation. The number of labeled cells and intensity of hybridization signal was greatest during the first 2 postnatal weeks, a period of rapid neuronal proliferation in these regions. At the end of the first month, when neurogenesis had essentially ceased, IGF-1 signal strength had declined to background levels. The temporal and spatial pattern IGF-1 mRNA expression in the immature CNS was consistent with a role for locally produced IGF-1 in the regulation of brain development.

Aging↗