An Environmental Law Even Judge Learned Hand Would Violate: Ohio EPA Needs Non-Monetary Penalties to Enforce Construction NPDES Permits

The Ohio EPA regulates construction sites by issuing NPDES permits that impose restrictions on the discharge of stormwater. Construction sites, however, have little incentive to follow these requirements. For many construction sites, it is more economical to be out of compliance and risk an unlikely fine than to comply with the permit. When these construction sites are out of compliance, stormwater runoff carries sediment into waterways and adversely affects water quality. In negligence torts, the Learned Hand Formula is used to determine what a reasonable person would do. The Learned Hand Formula, when applied to what an economically reasonable construction company would do, indicates that violating the NPDES permit is in a construction company\u27s best economic interest. While probably not actually thinking through the application of the Learned Hand Formula, construction companies are reaching this same conclusion. Therefore, construction companies need stronger disincentives not to violate their permits. To achieve this, the Ohio EPA needs to be able to utilize non-monetary enforcement methods because the current enforcement of the general construction NPDES permit does not effectively encourage compliance. Part II of this article discusses the damage sediment inflicts on waterways and ecosystems. Part III provides an overview of the NPDES program, including examples of the typical violations that Ohio EPA auditors find on construction sites. Part IV reviews the US EPA\u27s stormwater enforcement strategy. Part V shows the number of construction sites that are out of compliance with the NPDES permit and demonstrates why those construction sites do not have the incentive to comply. Part VI establishes that monetary penalties alone cannot be an effective deterrent to noncompliance. Part VII discusses several types of nonmonetary penalties, whether they are available to the U.S. EPA, Ohio EPA, or local governments, and whether those non-monetary penalties are likely to be an effective deterrent

Trim5 TAKes on Pattern Recognition

Retroviral capsids can be recognized and degraded by a host protein, Trim5α. A recent study in Nature (Pertel et al., 2011) shows that, upon sensing of the retrovirus capsid lattice, Trim5α generates free ubiquitin chains that activate the TAK1 kinase and downstream innate immune response genes

Human Trim5α has additional activities that are uncoupled from retroviral capsid recognition

AbstractTrim5α is a host antiviral protein that recognizes incoming retroviral capsids in the cytoplasm and prevents productive infections. Although present in most mammals, the state of the Trim5 gene is dynamic in that primates have one copy with several splice variants, while rodents and cows have multiple copies. Mouse Trim30 (one of the mouse Trim5α homologs) has been shown to negatively regulate NF-kappaB activation by targeting upstream signaling intermediates TAB2 and TAB3 for degradation. We show that human Trim5α also affects levels of TAB2, resulting in abrogation of TAB2-dependent NF-kappaB activation. Surprisingly, unlike mouse Trim30, human and rhesus Trim5α are able to activate NF-kappaB-driven reporter gene expression in a dose-dependent manner. We show that Trim5α uses distinct domains for the distinct abilities of affecting TAB2 levels, regulating NF-kappaB, and recognizing retroviral capsids. Our results demonstrate functions of Trim5α that are not dependent on recognizing the retroviral capsid

The Cell Cycle Independence of HIV Infections Is Not Determined by Known Karyophilic Viral Elements

Human immunodeficiency virus and other lentiviruses infect cells independent of cell cycle progression, but gammaretroviruses, such as the murine leukemia virus (MLV) require passage of cells through mitosis. This property is thought to be important for the ability of HIV to infect resting CD4+ T cells and terminally differentiated macrophages. Multiple and independent redundant nuclear localization signals encoded by HIV have been hypothesized to facilitate migration of viral genomes into the nucleus. The integrase (IN) protein of HIV is one of the HIV elements that targets to the nucleus; however, its role in nuclear entry of virus genomes has been difficult to describe because mutations in IN are pleiotropic. To investigate the importance of the HIV IN protein for infection of non-dividing cells, and to investigate whether or not IN was redundant with other viral signals for cell cycle-independent nuclear entry, we constructed an HIV-based chimeric virus in which the entire IN protein of HIV was replaced by that of MLV. This chimeric virus with a heterologous IN was infectious at a low level, and was able to integrate in an IN-dependent manner. Furthermore, this virus infected non-dividing cells as well as it infected dividing cells. Moreover, we used the chimeric HIV with MLV IN to further eliminate all of the other described nuclear localization signals from an HIV genome—matrix, IN, Viral Protein R, and the central polypurine tract—and show that no combination of the virally encoded NLS is essential for the ability of HIV to infect non-dividing cells

Iowa\u27s Sand Prairie State Preserves: Anomalous Grain-Size Distributions and Optically Stimulated Luminescence (OSL) Dates

Grain-size distributions and optically stimulated luminescence (OSL) dates were obtained for the sand from Iowa\u27s five sand prairie state preserves, which are Behren\u27s Ponds and Woodland, Cedar Hills Sand Prairie, Kish-Ke-Kosh Prairie, Marietta Sand Prairie and Rock Island. OSL dates ranged from the late Pleistocene (15,560 years B.P.) to the very late Holocene (as recent as 590 years B.P.), indicating that the late Pleistocene and Holocene Epochs in Iowa have seen multiple episodes of aridity, which is consistent with results from the Nebraska Sand Hills and eolian sand stringers in southeastern Minnesota. The grain-size distributions were anomalous in that, compared with typical eolian deposits, the transition grain sizes between the traction I saltation populations and saltation I suspension populations were shifted toward coarser grains, and the percentage of sand in the suspension population was high. The anomalous grain-size distributions could not be explained by post-depositional weathering or poor sorting in the source region, but were consistent with the eolian transport of sand through grass prior to deposition. It is suggested that the anomalous grain-size distribution could be one of a set of criteria for distinguishing paleo-sand prairies from other buried bodies of eolian sand or sandstone

Discordant Evolution of the Adjacent Antiretroviral Genes TRIM22 and TRIM5 in Mammals

TRIM5α provides a cytoplasmic block to retroviral infection, and orthologs encoded by some primates are active against HIV. Here, we present an evolutionary comparison of the TRIM5 gene to its closest human paralogs: TRIM22, TRIM34, and TRIM6. We show that TRIM5 and TRIM22 have a dynamic history of gene expansion and loss during the evolution of mammals. The cow genome contains an expanded cluster of TRIM5 genes and no TRIM22 gene, while the dog genome encodes TRIM22 but has lost TRIM5. In contrast, TRIM6 and TRIM34 have been strictly preserved as single gene orthologs in human, dog, and cow. A more focused analysis of primates reveals that, while TRIM6 and TRIM34 have evolved under purifying selection, TRIM22 has evolved under positive selection as was previously observed for TRIM5. Based on TRIM22 sequences obtained from 27 primate genomes, we find that the positive selection of TRIM22 has occurred episodically for approximately 23 million years, perhaps reflecting the changing pathogenic landscape. However, we find that the evolutionary episodes of positive selection that have acted on TRIM5 and TRIM22 are mutually exclusive, with generally only one of these genes being positively selected in any given primate lineage. We interpret this to mean that the positive selection of one gene has constrained the adaptive flexibility of its neighbor, probably due to genetic linkage. Finally, we find a striking congruence in the positions of amino acid residues found to be under positive selection in both TRIM5α and TRIM22, which in both proteins fall predominantly in the β2-β3 surface loop of the B30.2 domain. Astonishingly, this same loop is under positive selection in the multiple cow TRIM5 genes as well, indicating that this small structural loop may be a viral recognition motif spanning a hundred million years of mammalian evolution

Positive Selection and Increased Antiviral Activity Associated with the PARP-Containing Isoform of Human Zinc-Finger Antiviral Protein

Intrinsic immunity relies on specific recognition of viral epitopes to mount a cell-autonomous defense against viral infections. Viral recognition determinants in intrinsic immunity genes are expected to evolve rapidly as host genes adapt to changing viruses, resulting in a signature of adaptive evolution. Zinc-finger antiviral protein (ZAP) from rats was discovered to be an intrinsic immunity gene that can restrict murine leukemia virus, and certain alphaviruses and filoviruses. Here, we used an approach combining molecular evolution and cellular infectivity assays to address whether ZAP also acts as a restriction factor in primates, and to pinpoint which protein domains may directly interact with the virus. We find that ZAP has evolved under positive selection throughout primate evolution. Recurrent positive selection is only found in the poly(ADP-ribose) polymerase (PARP)–like domain present in a longer human ZAP isoform. This PARP-like domain was not present in the previously identified and tested rat ZAP gene. Using infectivity assays, we found that the longer isoform of ZAP that contains the PARP-like domain is a stronger suppressor of murine leukemia virus expression and Semliki forest virus infection. Our study thus finds that human ZAP encodes a potent antiviral activity against alphaviruses. The striking congruence between our evolutionary predictions and cellular infectivity assays strongly validates such a combined approach to study intrinsic immunity genes

An expanded clade of rodent Trim5 genes

AbstractTrim5α from primates (including humans), cows, and rabbits has been shown to be an active antiviral host gene that acts against a range of retroviruses. Although this suggests that Trim5α may be a common antiviral restriction factor among mammals, the status of Trim5 genes in rodents has been unclear. Using genomic and phylogenetic analyses, we describe an expanded paralogous cluster of at least eight Trim5-like genes in mice (including the previously described Trim12 and Trim30 genes), and three Trim5-like genes in rats. Our characterization of the rodent Trim5 locus, and comparison to the Trim5 locus in humans, cows, and rabbits, indicates that Trim5 has undergone independent evolutionary expansions within species. Evolutionary analysis shows that rodent Trim5 genes have evolved under positive selection, suggesting evolutionary conflicts consistent with important antiviral function. Sampling six rodent Trim5 genes failed to reveal antiviral activities against a set of eight retroviral challenges, although we predict that such activities exist