Search

Federal regulations for municipal separate storm sewer systems (MS4s) in the United States have been in place since 1990 as part of the Nation Pollutant Discharge Elimination System (NPDES), aiming to reduce sediment and pollutant loads originating from urban areas. However, small-municipality (Phase II) MS4s frequently grapple with several challenges, resulting in a lack of stakeholder buy-in and actionable stormwater management plans. We identify five common challenges concerning MS4 requirements based on literature review, professional experience, and feedback solicited from stakeholders, municipal managers, and fellow professionals and offer real-world examples of efficient, effective MS4 frameworks and/or solutions. The five challenges are summarized as beliefs that: (1) agricultural land use is the largest pollutant contributor and the root cause of pollution problems; (2) stormwater management only benefits downstream communities; (3) large, expensive projects are required to comply with regulations; (4) maintenance, monitoring, and inspection of best management practices (BMPs) is overwhelmingly complex and expensive; and (5) a lack of direct funding makes complying with regulations an impossible task. These challenges are universal in nature for Phase II MS4 permittees and can create real barriers for effective stormwater management. However, we found many examples of methods or techniques to effectively address these five specific challenges, making them well-suited and important for discussion. BMPs can create tangible improvements for surrounding communities (e.g., reduced streambank erosion and flooding), and improved understanding of the structure and options within the MS4 program will help small municipalities make informed choices about management plans.

The study aim was to characterise issues faced by farmers and veterinary surgeons when making end-of-life decisions for dairy cattle.Online surveys were distributed to British dairy farmers and veterinary surgeons for 20 weeks from November 2020.There were 83 responses (37 farmers, 46 veterinary surgeons). Among youngstock, the risk of unassisted/natural death (2.6% ± 0.3%) was almost double the risk of euthanasia (1.4% ± 0.3%;The survey highlighted end-of life decision-making successes and areas for improvement on dairy farms. An evidence-based, decision-support framework may help end-of-life decision-making, particularly for complex diseases.

Este artículo contiene 16 páginas, 2 tablas, 3 figuras., Urban streams can provide amenities to people living in cities, but those benefits are reduced when streams become degraded, potentially even causing harm (disease, toxic compounds, etc.). Governments and institutions invest resources to improve the values and services provided by urban streams; however, the conception, development, and implementation of such projects may not include meaningful involvement of community members and other stakeholders. Consequently, project objectives may be misaligned with community desires and needs, and projects may fail to achieve their goals. In February 2020, the 5th Symposium on Urbanization and Stream Ecology, an interdisciplinary meeting held every 3 to 5 y, met in Austin, Texas, USA, to explore new approaches to urban stream projects, including ways to maximize the full range of potential benefits by better integrating community members into project identification and decision making. The symposium included in-depth discussion about 4 nearby field case studies, participation of multidisciplinary urban stream experts from 5 continents, and input from the Austin community. Institutional barriers to community inclusion were identified and analyzed using real-world examples, both from the case studies and from the literature, which clarified disparities in power, equity, and values. Outcomes of the symposium have been aggregated into a vision that challenges the present institutional approach to urban stream management and a set of strategies to systematically address these barriers to improve restoration solutions. Integrating community members and other stakeholders throughout the urban restoration process, and a transparent decision-making process to resolve divergent objectives, can help identify appropriate goals for realizing both the ecological and social benefits of stream restoration., Publication costs were covered by an award from the Society of Freshwater Science’s Endowed Publication Fund (https:// freshwater-science.org/publications/endowed-publication-fund).

Simple Summary Stream insects are essential components of aquatic and terrestrial ecosystems, but fewer studies have examined the terrestrial stage compared to the aquatic stage. Most adult stream insects are flight capable, which allows for short- and long-distance movements away from the stream channel into riparian or upland habitats. This study examined if adult stream insects migrate vertically into riparian forest canopies above the stream. We found a meaningful number of adult Trichoptera and Plecoptera in the forest canopy above the stream that was comparable to horizontal migrations. This result demonstrated that adult stream insects utilize riparian forest canopies and that numerous avenues for additional basic and applied research on terrestrial–aquatic linkages exist. Discovering how riparian canopy habitats are important for stream insects and how stream insects are linked to canopy ecosystems can inform restoration and conservation actions. Abstract Stream insects are essential components of aquatic and terrestrial ecosystem structure and function. Terrestrial stages are important components of terrestrial food webs, and flight-capable individuals are responsible for long-distance dispersal. Horizontal migrations by flying or crawling adults away from stream channels that link insects to riparian food webs and movements across catchment boundaries are well established through empirical research, but studies examining vertical migration of adult stream insects into forest canopies are generally lacking. This study focused on differences in adult Plecoptera and Trichoptera abundance at ground level versus the riparian canopy and differences in abundances among summer and autumn sampling periods to empirically demonstrate use of canopy ecosystems by stream insects. Malaise traps at ground level and canopy traps placed 8 to 10 m above the stream at four sites in the Mosquito Creek watershed (Pennsylvania) were used to examine vertical migration. Larval assemblages were collected and compared to adult assemblage to investigate patterns of local migration in the catchment. We found significantly more stream insects at ground level than in the forest canopy for Trichoptera, Plecoptera, and all individual plecopteran families, but a meaningful number of individuals were found in the riparian canopy. Canopy abundances were similar to abundances captured in adjacent ground-level habitats in other studies. Comparisons of adult and larval abundances among sites, taxa, and stages indicated site- and taxon-specific patterns for vertical movement into riparian canopies. Demonstrating that adult stream insects utilize riparian forest canopies indicates that riparian forest conservation should be prioritized over reforestation and that several potential research questions exist to inform riparian management.

3-Hydroxy-4-pyridinones and 5-hydroxy-4-pyrimidinones were identified as inhibitors of catechol-O-methyltransferase (COMT) in a high-throughput screen. These heterocyclic catechol mimics exhibit potent inhibition of the enzyme and an improved toxicity profile versus the marketed nitrocatechol inhibitors tolcapone and entacapone. Optimization of the series was aided by X-ray cocrystal structures of the novel inhibitors in complex with COMT and cofactors SAM and Mg(2+). The crystal structures suggest a mechanism of inhibition for these heterocyclic inhibitors distinct from previously disclosed COMT inhibitors.

Epigenetic modifications play a crucial role in human diseases. Unlike genetic mutations, however, they do not change the underlying DNA sequences. Epigenetic phenomena have gained increased attention in the field of cancer research, with many studies indicating that they are significantly involved in tumor establishment and progression. Histone methyltransferases (HMTs) are a large group of enzymes that specifically methylate protein lysine and arginine residues, especially in histones, using S-adenosyl-L-methionine (SAM) as the methyl donor. However, in general, HMTs have no widely accepted high-throughput screening (HTS) assay format, and reference inhibitors are not available for many of the enzymes. In this study, we describe the application of a miniaturized, radioisotope-based reaction system: the HotSpot(SM) platform for methyltransferases. Since this platform employs tritiated SAM as a cofactor, it can be applied to the assay of any HMT. The key advantage of this format is that any substrate can be used, including peptides, proteins, or even nucleosomes, without the need for labeling or any other modifications. Using this platform, we have determined substrate specificities, characterized enzyme kinetics, performed compound profiling for both lysine and arginine methyltransferases, and carried out HTS for a small-library LOPAC against DOT1L. After hit confirmation and profiling, we found that suramin inhibited DOT1L, NSD2, and PRMT4 with IC₅₀ values at a low μM range.

STUDY OBJECTIVE—To examine the relation of antioxidant and other nutrient intakes in pregnancy to smoking and sociodemographic variables. DESIGN—Cohort study. SETTING—St Mary's Maternity Hospital, Portsmouth. PARTICIPANTS—Pregnant nulliparous women, with no existing complications of pregnancy, were recruited from antenatal booking clinics. A total of 774 women completed seven day food diaries, and supplied detailed data on their use of nutrient supplements. MAIN RESULTS—Smokers had lower intakes of most micronutrients. After adjustment for the confounding effects of maternal age, height, and education, only vitamin C and carotenoid intakes remained significantly depressed. Age was strongly and significantly associated with the intake of most nutrients, including antioxidants, and this association was independent of other maternal factors. Antioxidant intake was therefore lowest in young women who smoked: for example smokers under 24 years had a mean vitamin C intake of 57 mg (SD 35) compared with 106 mg (SD 52) for non-smokers aged 28 and over (difference 49 mg, 95% CI 39, 59). The corresponding intakes of carotenoid equivalents were 1335 µg (SD 982) and 2093 µg (SD 1283) (difference 758 µg, 95% CI 496, 1020). CONCLUSIONS—The study has identified, for the first time, young pregnant women as a group at particular risk of low micronutrient intake. The health implications of poor nutrition now need to be evaluated, particularly for those women who smoke. Keywords: pregnancy; nutrition; age

Pervasive human impacts on urban streams make restoration to predisturbance conditions unlikely. The effective- ness of ecologically focused restoration approaches typically is limited in urban settings because of the use of a reference-condition approach, mismatches between the temporal and spatial scales of impacts and restoration activities, and lack of an integrative ap- proach that incorporates ecological and societal objectives. Developers of new frameworks are recognizing the opportunities for and benefits from incorporating societal outcomes into urban stream restoration projects. Social, economic, cultural, or other benefits to local communities are often opportunistic or arise indirectly from actions intended to achieve ecological outcomes. We propose urban stream renovation as a flexible stream improvement framework in which short-term ecological and societal outcomes are leveraged to achieve long-term ecological objectives. The framework is designed to provide additional opportunities for beneficial outcomes that are often unattainable from ecologically focused restoration approaches. Urban stream renovation uses an iterative process whereby short-term ecological and societal outcomes generate public support for future actions, which may provide opportunities to address catchment-level causes of impairment that often exist across broad temporal scales. Adaptive management, education, and outreach are needed to maintain long-term public engagement. Thus, future work should focus on understanding how ecological and societal contexts interact, how to assess societal outcomes to maintain stewardship, developing new methods for effective education and outreach, and multidisciplinary collaborations. We discuss potential abuses and the im- portance of linking societal outcomes to long-term ecological objectives.

Agricultural drainage ditches are artificial structures used to optimize soil hydrology for crop production and secondarily have been co-opted as a tool to manage the quality of water draining from agricultural lands. We investigated the relationship between the aquatic macroinvertebrate community and environmental variables associated with physical and biogeochemical processes that affect water quality. Aquatic macroinvertebrates were sampled along with physical and chemical measures of the soil and water from 29 agricultural drainage ditches on the Eastern Shore of Maryland. Cluster analysis and multivariate ordination showed that ditches that had higher flow velocities supported communities of lotic invertebrates (i.e., Stenelmis, Prosimulium) versus those that had properties of linear wetlands, which supported communities of lentic invertebrates (i.e., Oligochaeta, Caecidotea). Taxon richness varied from four to 31 taxa per ditch, and was higher within ditches that had higher flow velocities....

Reduced dopamine neurotransmission in the prefrontal cortex has been implicated as causal for the negative symptoms and cognitive deficit associated with schizophrenia; thus, a compound which selectively enhances dopamine neurotransmission in the prefrontal cortex may have therapeutic potential. Inhibition of catechol-O-methyltransferase (COMT, EC 2.1.1.6) offers a unique advantage, since this enzyme is the primary mechanism for the elimination of dopamine in cortical areas. Since membrane bound COMT (MB-COMT) is the predominant isoform in human brain, a high throughput screen (HTS) to identify novel MB-COMT specific inhibitors was completed. Subsequent optimization led to the identification of novel, non-nitrocatechol COMT inhibitors, some of which interact specifically with MB-COMT. Compounds were characterized for in vitro efficacy versus human and rat MB and soluble (S)-COMT. Select compounds were administered to male Wistar rats, and ex vivo COMT activity, compound levels in plasma and cerebrospinal fluid (CSF), and CSF dopamine metabolite levels were determined as measures of preclinical efficacy. Finally, novel non-nitrocatechol COMT inhibitors displayed less potent uncoupling of the mitochondrial membrane potential (MMP) compared to tolcapone as well as nonhepatotoxic entacapone, thus mitigating the risk of hepatotoxicity.

Adult dispersal and completion of life cycles by aquatic insects are essential for the persistence of populations, colonization of new habitats, and maintenance of genetic diversity. However, life-cycle stages and processes associated with the terrestrial environment often are overlooked when the effect of watershed urbanization on the persistence of insects associated with streams is examined. We reviewed and synthesized current literature on the known effects of watershed urbanization on the terrestrial stage of stream insects. Some research has directly examined the effects of watershed urbanization on dispersal, but much of the evidence we present is indirect and from related studies on aquatic insect life-history traits and dispersal abilities in nonurban watersheds. Our goal is to provide examples of potential impacts that warrant further study, rather than to provide a comprehensive review of all life-history studies. We discuss how watershed land use, riparian condition, and habitat qualit...

SUMMARY Exposure to anesthetic drugs during gestation has been shown to cause behavioral changes in rats, and exposure during labor and delivery also affects human neonatal behavior. In this preliminary study, nine neonates who had been exposed to anesthetic agents during gestation were tested for visual-pattern preference. These nine infants looked at the stimuli for statistically significantly longer periods compared with 30 non-exposed infants. and had significantly different preferences for some pairs of patters. The results suggest that prenatal exposure to anesthetic agents may contribute to behavioral alterations in human neonates. RESUME La preference neonatale de patterns visuels est-elle modifiee par une exposition prenatale a une anesthesie? II a ete montre qu'une exposition durant la gestation a des drogues anesthesiques provoquait des modifications de comportement chez le rat et que cette exposition durant le travail ou I'accouchement affectait egalement Ie comportement humain neo-natal. Dans ectteetude preliminaire. neuf nouveau-nes exposes a des agents anesthesiques durant la grosscsse ont ete testes a la recherche de preferences de patterns visuels. Les neuf nourrissons ont regarde les stimuli duranl des periodes significativement plus longues par comparaison avcc des 30 nourrissons non exposes et presentaient des preerences significativement differentes pour quelques pairs de patterns. Ces resultats suggerent que I'exposition prenatale a des agents anesthesiques peut favoriser des alterations comportementales chez les nouveau-nes humains. ZUSAMMENFASSUNG Wird die Praferenz visueller Muster beim Neugeborenen durch die pranatale Exposition zu Anasthelika veranderr? Die Exposition zu Anasthetika wahrend der Gestationsphase hat bei Ratten zu Verhaltensveranderungen gefuhrt und eine Exposition wahrend der Wehen und unter der Geburt beeinflust auch das Verhalten der Neugeborenen. Bci dieser vorlaufigen Studie wurden neun Neugeborene. die wahrend der Gestationszeit eine Exposition zu Anashetika hatten, auf ihre Praferenz visueller Muster getestet. Die neun Kindern betrachteten die Stimuli statistisch signifikant langer verglichen mil 30 nicht exponierten Kindern und hatten signifikant unterschiedliche Praferenzen fur einige Muster. Die Ergebnisse lassen vermuten. dap die pranatale Exposition zu Anasthetika bei Neugeborenen Verhaltensveranderungen hervorrufen kann. RESUMEN ?Esta el esquema de preferencia visual neonaral modificado por la exposicion neonatal a la anestesia? Se ha visto que la exposicion a farmacos anestesicos durante la gestacion causa cambios en el comportamiento de las ratas, y la exposicion durante el parto tambien afecta al comportamiento del recien nacido humano. En este estudio preliminar, neuve recien nacidos que habian sido expuestos a agentes anestesicos durdnte la gestacion fueron examinados en su esquema de preferencia visual. Los neuve ninos miraban a los estimulos durante un ticmpo significativamente mayor en comparacion con los 30 ninos no expuestos y tenian unas preferencias significativamente diferentes para algunos pares de esquemas. Los resultados sugiere que la exposicon prenatal a agentes anntesicos puede contribuir a alteraciones de comportamiento en el recien nacido humano.

Bees of the genusOsmiaPanzer (Hymenoptera: Megachilidae) are among the contenders to replace honey bees,Apis melliferaL. (Apidae), for pollinating tree-fruit crops. One species,Osmia lignariaSay, has shown great potential in western North America and was recently introduced into Nova Scotia for evaluation as a pollinator of apple,MalusMill. (Rosaceae). A major component of that study was to develop management options forO. lignaria, including methods of sustaining nesting females following crop flowering to maximize population recovery for pollination in subsequent seasons. The objective of this study was to evaluate bigleaf lupine,Lupinus polyphyllusLindl. (Fabaceae), as a secondary food plant for nesting femaleO. lignariaby investigating nesting activity, pollen-use patterns, and fecundity. During 2002–2003, femaleO. lignariacollected high proportions of apple pollen (>70%) during mid and late flowering; after then, most pollen (>90%) was collected from bigleaf lupine. The flowering period of lupine in Nova Scotia (late May to early July) slightly overlapped that of apple, so there was no scarcity of pollen resources during the life-span ofO. lignaria. Most nests typically showed high levels (≤200%) of population growth, but recorded levels varied among nest types and locations. In 2004, nests closer to lupine plots exhibited significantly greater population recovery than nests located farther away (i.e., approximately 600 m). Bigleaf lupine is a suitable plant species for meeting the pollen requirements of nesting populations ofO. lignariafollowing apple flowering, thus promoting the recovery of populations to meet apple pollination requirements in subsequent seasons.

Watershed urbanization decreases diversity and taxonomic richness of aquatic insect communities, and headwater streams are particularly susceptible to degradation from urbanization. Patterns of taxon loss between urban headwater communities and communities in adjacent downstream, higher-order reaches might indicate which processes are controlling taxon loss and the extent to which unique headwater taxa are lost after urbanization. We compared insect communities in urban and rural watersheds and investigated if community similarity between headwater streams and adjacent higher-order main-stem reaches was greater in urban than in rural watersheds. We sampled insect communities in 3 urban and 3 rural watersheds in Maryland's Piedmont region during 3 seasons. Mean taxonomic richness was 4.33 greater and the Shannon diversity index was 1.83 greater in rural than in urban headwater streams. Simpson's index was 1.93 greater in urban than in rural headwater streams. The Jaccard similarity index calculated between headwater and main-stem communities was 1.63 greater for urban sites than rural sites during autumn, and the proportion of headwater taxa shared with the main-stem community was 1.83 greater for urban than rural sites. Redundancy analysis also indicated significantly greater similarity between urban headwater and main-stem communities than between rural headwater and main-stem communities. As expected, urbanization decreased diversity, and the communities remaining in urban headwaters were mostly subsets of the communities in the main-stem streams. This result suggested that taxa unique to headwaters were at the greatest risk of local extirpation after watershed urbanization. A significant interactive effect of landuse type and the longitudinal position of a reach along the headwater on taxonomic richness and the Jaccard index suggested that patterns of taxon loss partially depended on the proximity of a headwater reach to the main-stem stream. Overall, the results suggested that water- and habitat-quality degradation were not the only effects of watershed urbanization that determined the composition of insect communities in urban headwaters.

Methylation of histone H3 lysine-4 (H3K4) is an important, regulatory, epigenetic post-translational modification associated with actively transcribed genes. In humans, the principal mediators of this modification are part of the MLL/SET1 family of methyltransferases, which comprises six members, MLLs1-4 and SET1A/SET1B. Aberrations in the structure, expression, and regulation of these enzymes are implicated in various disease states, making them important potential targets for drug discovery, particularly for oncology indications. The MLL/SET1 family members are most enzymatically active when part of a "core complex," the catalytic SET-domain-containing subunits bound to a subcomplex consisting of the proteins WDR5, RbBP5, Ash2L and a homodimer of DPY-30 (WRAD2). The necessity of MLL/SET1 members to bind WRAD2 for full activity is the basis of a particular drug development strategy, which seeks to disrupt the interaction between the MLL/SET1 subunits and WDR5. This strategy is not without its theoretical and practical drawbacks, some of which relate to the ease with which complexes of Escherichia coli-expressed MLL/SET1 and WRAD2 fall apart. As an alternative strategy, we explore ways to stabilize the complex, focusing on the use of an excess of WRAD2 to drive the binding equilibria toward complex formation while maintaining low concentrations of the catalytic subunits. The purpose of this approach is to seek inhibitors that bind the SET domain, an approach proven successful with the related, but inherently more stable, enhancer of zeste homolog 2 (EZH2) complex.

The flight activity of the apple leaf midge, Dasineura mali (Kieffer), was determined in the field and laboratory. Males and females began emerging at the onset of the photophase. In the field, delta-shaped traps baited with 6 virgin females caught males exclusively, with the most abundant catches on the ground as compared to those at 1 and 2 m. Most males were captured at 1100 hours and males remained in the vegetation under the trees throughout the day. Sweep netting revealed that conspecifics mate in the vegetation under orchard trees in the morning hours, and females move from the ground to the orchard canopy to oviposit at 1000 hours. Gas chromatographic-electroantennographic detection (GC-EAD) analyses indicated the presence of an electrophysiologically active compound in solid phase microextraction (SPME) effluvial collections and pheromone gland extractions from virgin females.

Cells in the medial preoptic area (mPOA), arcuate nucleus (ARC), and ventromedial nucleus (VMN) that possess estrogen receptor alpha (ER alpha) mediate estradiol feedback to regulate endocrine and behavioral events during the estrous cycle. A percentage of ER alpha cells located in the ARC and VMN express somatostatin (SST) and are activated in response to estradiol. The aims of the present study were to investigate the location of c-Fos, a marker for activation, in cells containing ER alpha or SST at various times during the follicular phase and to determine whether lipopolysaccharide (LPS) administration, which leads to disruption of the luteinizing hormone (LH) surge, is accompanied by altered ER alpha and/or SST activation patterns. Follicular phases were synchronized with progesterone vaginal pessaries, and control animals were killed at 0, 16, 31, and 40 h (n = 4-6/group) after progesterone withdrawal (PW [time 0]). At 28 h, other animals received LPS (100 ng/kg) and were subsequently killed at 31 h or 40 h (n = 5/group). Hypothalamic sections were immunostained for c-Fos and ER alpha or SST. LH surges occurred only in control ewes with onset at 36.7 ± 1.3 h after PW; these animals had a marked increase in the percentage of ER alpha cells that colocalized c-Fos (%ER alpha/c-Fos) in the ARC and mPOA from 31 h after PW and throughout the LH surge. In the VMN, %ER alpha/c-Fos was higher in animals that expressed sexual behavior than in those that did not. SST cell activation in the ARC and VMN was greater during the LH surge than in other stages in the follicular phase. At 31 or 40 h after PW (i.e., 3 or 12 h after treatment, respectively), LPS decreased %ER alpha/c-Fos in the ARC and the mPOA, but there was no change in the VMN compared to that in controls. The %SST/c-Fos increased in the VMN at 31 h after PW (i.e., 3 h after LPS) with no change in the ARC compared to controls. These results indicate that there is a distinct temporal pattern of ER alpha cell activation in the hypothalamus during the follicular phase, which begins in the ARC and mPOA at least 6-7 h before the LH surge onset and extends to the VMN after the onset of sexual behavior and LH surge. Furthermore, during the surge, some of these ER alpha-activated cells may be SST-secreting cells. This pattern is markedly altered by LPS administered during the late follicular phase, indicating that the disruptive effects of this stressor are mediated by suppressing ER alpha cell activation at the level of the mPOA and ARC and enhancing SST cell activation in the VMN, leading to the attenuation of the LH surge.

Bacterial resistance is eroding the clinical utility of existing antibiotics necessitating the discovery of new agents. Bacterial type II topoisomerase is a clinically validated, highly effective, and proven drug target. This target is amenable to inhibition by diverse classes of inhibitors with alternative and distinct binding sites to quinolone antibiotics, thus enabling the development of agents that lack cross-resistance to quinolones. Described here are novel bacterial topoisomerase inhibitors (NBTIs), which are a new class of gyrase and topo IV inhibitors and consist of three distinct structural moieties. The substitution of the linker moiety led to discovery of potent broad-spectrum NBTIs with reduced off-target activity (hERG IC5018 μM) and improved physical properties. AM8191 is bactericidal and selectively inhibits DNA synthesis and Staphylococcus aureus gyrase (IC50 = 1.02 μM) and topo IV (IC50 = 10.4 μM). AM8191 showed parenteral and oral efficacy (ED50) at less than 2.5 mg/kg doses in a S. aureus murine infection model. A cocrystal structure of AM8191 bound to S. aureus DNA-gyrase showed binding interactions similar to that reported for GSK299423, displaying a key contact of Asp83 with the basic amine at position-7 of the linker.

To determine whether cocaine administration during a developmental period corresponding to middle and late childhood results in enduring changes in behavior, we injected rats with 5 or 20 mg/kg/d of cocaine s.c. from weaning (postnatal day 21; P21) through P60; controls included uninjected and vehicle-injected controls. The 20-mg/kg dose resulted in a transient, male-limited weight reduction for the last 10 days of dosing, which rapidly recovered to normal after dosing ceased. Approximately 5 months later, the subjects were given a brief battery of behavioral tests. Female 20-mg subjects received fewer reinforcements than control subjects in a DRL-20 task. Female subjects also displayed altered patterns of cocaine-stimulated changes in open-field activity. No significant lasting effects were seen in males. These data suggest that the central nervous system retains sufficient plasticity into later development to produce long-lasting functional changes in response to drug administration and that cocaine consumption during the rat equivalent of childhood produces very long lasting plastic changes in behavior.

We investigated the utility of maternal cotinine concentration as a predictor of preterm and small-for-gestational-age (SGA) deliveries. Subjects were randomly selected from antenatal clinics, and their serum cotinine concentrations at approximately 16 weeks' gestation were compared with self-reports of smoking. The value of these measures in predicting preterm and SGA deliveries was examined, using likelihood ratios and logistic regression, for 845 women with singleton, live births. Smoking status alone (defined by self-report or cotinine) only weakly predicted preterm or SGA delivery. Self-reported moderate/high smoking (top 15% of smokers) had a likelihood ratio (LR) of 2 and a positive predictive value (PPV) of 17%. In contrast, moderate/high cotinine concentration (top 15% of smokers) had an LR of 5 and a PPV of 33%. The predictive value of cotinine was independent of associated maternal characteristics. Cotinine concentration may therefore be a useful predictor of poor pregnancy outcome, and should be considered as a screening tool.

The performance of a simple colorimetric assay for urinary nicotine metabolites to assess smoking status in diabetic subjects (n = 251) was investigated. Several variations of the colorimetric assay and a qualitative extraction procedure were evaluated in comparison with a cotinine immunoassay as the “gold standard.” Among these, the best overall performance was achieved with the qualitative test (sensitivity 95%; specificity 100%). The quantitative measurement of total nicotine metabolites performed less well (sensitivity 92%; specificity 97%) but could be improved by incorporating a blank extraction (sensitivity 98%; specificity 98%). Allowance for diuresis appeared to offer no advantage over the other methods. These results support previous findings regarding the use of these colorimetric procedures in nondiabetic subjects and, contrary to other recent observations, their performance was not impaired in diabetic patients.

A typical Data Structures (CS 2) course covers a wide variety of topics: elementary algorithm analysis; data structures including dynamic structures, trees, tables, graphs, etc. ; large programming projects; and more advanced object-oriented concepts. Integrating these topics into assignments is a challenging task; educators often duplicate work done by others in re-inventing such assignments. At the same time, these assignments and large programs take time to develop and are often changed from semester to semester to preclude cheating. We report on a project that provides modules containing many kinds of programming and lab assignments which can be re-used across semesters with accessible and exciting application-oriented materials. Our project is a collaboration between a research and teaching oriented private university, a teaching oriented public university, and a teaching oriented historically black university. This helps ensure that the modules will be accessible to nearly all student populations. The modules developed are available electronically as hyper-text documents.

The Book of Mormon annals open in an ancient Near Eastern context. The archaeological-historical context is carefully outlined here within a systematic chronology that is tied to fixed, absolute dates of recorded astronomical events—particularly those from cuneiform eponym calendars. The resultant matrix allows those early Book of Mormon events to be understood in a rational, familiar, and meaningful way, i.e., in a biblical context. In addition, an excursus is devoted to understanding the Arabia of the Book of Mormon as the Lehite exiles must have known it. Throughout it is clear that the world depicted by the Book of Mormon dovetails remarkably well with what we know of the ancient Near East.

Three different methods for estimating the percentage of reduction in the diameter of the internal carotid artery (ie, stenosis) have been proposed in the literature. Further comparisons of the methods were carried out with the intent of recommending a current standard for determining the percentage of stenosis from angiograms. Angiograms from 112 patients were obtained. For each angiogram, stenosis was estimated in the manner of the European Carotid Surgery Trial (ECST method), the North American Symptomatic Carotid Endarterectomy Trial (NASCET method), and by a method using the common carotid artery lumen diameter (CC method). Although there is much discrepancy among the estimates of stenosis arising from the three different methods for any particular patient, it is possible to predict (on average) the percentage of stenosis from one method to another. The relationship between the NASCET and CC methods is linear, with a mean ratio of distal internal carotid artery to common carotid diameter of 0.62 (SD of 0.11). The variability in the diameter of the common carotid artery lumen stabilizes only beyond 2.5 common carotid diameter units (approximately 20 to 30 mm by conventional angiography) proximal to the bifurcation. Unexpectedly, the relationships between both the ECST and NASCET methods and ECST and CC methods were parabolic (P < .001). The reasons underlying these departures from linearity are uncertain. The comparability of our results with those reported in the literature regarding the CC and NASCET methods provides further evidence of the reproducibility of methods measuring anatomic features that can be visualized on an angiogram. Disease of the internal carotid artery is one of the important causes of ischemic symptoms. Measuring the narrowest portion of the internal artery relative to the normal portion of the same artery, well beyond the bulb, is a logical method. Moreover, benefits of carotid endarterectomy for patients with 70% to 99% stenosis as determined by the NASCET method have been well established in a clinical trial. Converting from the NASCET method to the CC method, given that the CC method is neither superior nor easier to calculate, is not recommended.

The influence of nutrient limitation on the quality of Scenedesmus acutus as food for Daphnia obtusa is examined. The nature and degree of nutrient limitation greatly influences the rate at which Daphnia converts Scenedesmus biomass into herbivore biomass. From high to low quality, Scenedesmus food is ranked moderately N limited, severely N limited, and severely P limited. Even a very high concentration (3 mg DW.liter-I) of low quality food yields slow Daphnia growth, and it appears that no amount of low quality food would support rapid Daphnia growth. Food-limited animals display lowered intercepts of length-weight regressions (prereproductive females), reduced rates of biomass gain (both males and females), increased ages at first reproduction, lowered clutch sizes, increased mortality, and lowered reproductive rate. The N and P contents and the N : P ratio of Scenedesmus all vary considerably under N and P limitation, while the N content (and possibly P content) of Daphnia is less variable and the N: P ratio of Daphnia is essentially constant. Clearance and feeding rates are lower on severely P-limited cells than on severely N-limited cells. These results indicate that the mineral nutrition of their algal food may influence the demographics of zooplankton herbivores to a degree not before realized.

HIV/AIDS continues to be a menace to public health. Several drugs currently on the market have successfully improved the ability to manage the viral burden in infected patients. However, new drugs are needed to combat the rapid emergence of mutated forms of the virus that are resistant to existing therapies. Currently, approved drugs target three of the four major enzyme activities encoded by the virus that are critical to the HIV life cycle. Although a number of inhibitors of HIV RNase H activity have been reported, few inhibit by directly engaging the RNase H active site. Here, we describe structures of naphthyridinone-containing inhibitors bound to the RNase H active site. This class of compounds binds to the active site via two metal ions that are coordinated by catalytic site residues, D443, E478, D498, and D549. The directionality of the naphthyridinone pharmacophore is restricted by the ordering of D549 and H539 in the RNase H domain. In addition, one of the naphthyridinone-based compounds was found to bind at a second site close to the polymerase active site and non-nucleoside/nucleotide inhibitor sites in a metal-independent manner. Further characterization, using fluorescence-based thermal denaturation and a crystal structure of the isolated RNase H domain reveals that this compound can also bind the RNase H site and retains the metal-dependent binding mode of this class of molecules. These structures provide a means for structurally guided design of novel RNase H inhibitors.

A simple electronic device to detect location or to track locomotion of small animals is described. The device is based on anantenna effect—it responds to a change in capacitance as the body of the animal passes between an antenna and one of a series of contact plates. A digital address system is incorporated that is capable of electronically polling the contact plates according to instructions from a data-acquisition system (DAS). Any DAS capable of generating an address of two bits or more and of reading a one-bit data line may be employed. The device is ideal for mazes or other apparatus in which the exclusion of stereotypical behaviors is desired.

p70 ribosomal S6 kinase (p70S6K) is a downstream effector of the mTOR signaling pathway involved in cell proliferation, cell growth, cell-cycle progression, and glucose homeostasis. Multiple phosphorylation events within the catalytic, autoinhibitory, and hydrophobic motif domains contribute to the regulation of p70S6K. We report the crystal structures of the kinase domain of p70S6K1 bound to staurosporine in both the unphosphorylated state and in the 3′-phosphoinositide-dependent kinase-1-phosphorylated state in which Thr-252 of the activation loop is phosphorylated. Unphosphorylated p70S6K1 exists in two crystal forms, one in which the p70S6K1 kinase domain exists as a monomer and the other as a domain-swapped dimer. The crystal structure of the partially activated kinase domain that is phosphorylated within the activation loop reveals conformational ordering of the activation loop that is consistent with a role in activation. The structures offer insights into the structural basis of the 3′-phosphoinositide-dependent kinase-1-induced activation of p70S6K and provide a platform for the rational structure-guided design of specific p70S6K inhibitors.

Cozart Bioscience Limited has developed novel lateral flow technology that allows the detection of drugs of abuse in biological fluids and suspect powders. This paper describes the application of this technology for the detection of 3,4-methylenedioxymethamphetamine (MDMA) in oral fluid. Samples (N = 370) were obtained from the analytical laboratory at Cozart Bioscience Limited following their routine analysis for drugs of abuse. Oral fluid samples were screened for the presence of MDMA and methamphetamine using the Cozart® RapiScan System (CRS) and then confirmed for the presence of amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA, and MBDB) by gas chromatography-mass spectrometry (GC-MS). In addition to the detection of MDMA and methamphetamine, the CRS cross-reacts with high levels of amphetamine to give a positive result. One hundred and twenty-one samples screened positive using the CRS. Six of these samples were confirmed negative for MDMA and methamphetamine, but contained very high levels of amphetamine. Employing a screening cutoff of 45 ng/mL for the CRS and a confirmation cutoff of 30 ng/mL for GC-MS, the sensitivity, specificity, and accuracy were 96.6, 96.8, and 96.8%, respectively. When applying the Substance Abuse and Mental Health Services Administration recommended confirmation cutoff for amphetamines of 50 ng/mL, the sensitivity, specificity, and accuracy increased marginally to 98.3, 96.9, and 97.3%, respectively.

In this experiment, we evaluated whether extinction of taste aversion following conditioning with a compound CS of visual and taste cues would attenuate taste-mediated aversion to visual cues. Sixty chicks (Gallus domesticus) received a pairing of a compound CS, red-colored water or red-colored vinegar, with a toxin and then extinction procedures with clear vinegar. Testing with red water showed reliable evidence of potentiation to visual cues in the red vinegar conditioning groups, as measured by latency to start drinking and intake performance. Taste-aversion extinction groups (n = 30), tested with clear vinegar, showed no reliable evidence of taste aversion. The results contradicted the within-compound hypothesis of taste-mediated potentiation and replicated Lett (1984).

Microscopists in today's laboratories face multiple challenges. Many must examine specimens according to legal, governmental or grant-specific requirements. Protocol requires that the specimens be documented by conventional photography, electronic imaging techniques, or both. Because of the thousands of specimens examined, operators work under conditions of potential physical strain for hours at a time. And the material they examine requires that they have expertise with large and complex imaging instruments.

Literature and drama are neglected but fruitful sources for economic instruction. They reflect and explicate major economic forces of their time.

An electronic device for detecting locomotor activity in the home cage of small animals is described. The system involves a dense array of infrared (IR) beams designed to function as switches and capable of penetrating plastic walls of standard rodent cages without operational decrement. The device is reasonably inexpensive, is simple to calibrate, can be used with groups of animals, may be used for extended periods without maintenance, and is reliable with different cages.

Previous authors have separately reported that the hyperreactivity syndrome commonly found after septal lesion can be attenuated by injection of either a serotonin depletor, PCPA, or a serotonin precursor, 5-HTP. The present experiment used a factorial design to investigate these apparently discrepant results. As previously reported, each drug produced a taming effect in septal animals, and additionally, the combination of the two drugs tended to have an additive, rather than an antagonistic, effect. This suggests that the two drugs might share a common neurochemical action. Since Sloviter, Drust, and Connor (1978) have reported that PCPA has an early serotonin-releasing effect, it appears that serotonin release, not depletion, has a taming effect in septal animals.

An electronic apparatus to detect vocalizations between 4 and 50 kHz and to provide frequency readout is described. A frequency-to-voltage converter changes vocalizations to their analog. A peak-and-hold circuit retains and gates the maximal value of this analog voltage while it is accessed by a chart recorder or computer. Provision is made to lock out noise by inhibiting the device’s response to all signals lower than those associated with a selectable cutoff frequency. In preliminary tests of the apparatus, vocal signals of two rats in a common cage were recorded while the animals were subjected to a brief, intermittent bout of faradic shock to the feet. All recorded vocalizations occurred at frequencies below 26 kHz.

Primary-care physicians often must decide when patients with asymptomatic microhematuria warrant further testing for renal parenchymal disease. Because previous data had shown a greater frequency of elevated serum creatinine concentration in a population with asymptomatic microhematuria than in control subjects without hematuria, we reviewed the records of 125 patients with isolated asymptomatic microhematuria and elevated serum creatinine (AM/EC) and 83 comparison patients with no hematuria and elevated serum creatinine (NH/EC) from a previous population-based study to determine the relationship between renal parenchymal disease and isolated asymptomatic microhematuria. Serum creatinine was often elevated transiently because of volume depletion or shock, or elevations occurred in relationship to a terminal illness. Thus, only 63 AM/EC patients and 45 NH/EC control subjects had primary renal parenchymal disease or systemic disorders that caused an elevated serum creatinine. The patients selected from the asymptomatic microhematuria population because of elevated serum creatinine most often had low-grade hematuria and were typically 75 years of age or older. No disease was consistently found more frequently in the AM/EC patients than in the NH/EC group. Intervention at the time of the detection of hematuria might have altered the prognosis in 8% and probably would not have altered the prognosis in 78%. Therefore, exhaustive diagnostic testing to detect renal parenchymal diseases cannot be advised in asymptomatic elderly patients with low-grade (grade 1) microhematuria unless more specific indications are present.

An electronic device that can detect discrete ambulatory and stereotypic behaviors of animals is described. The system involves a minimum of two infrared (IR) beams, each connected to a set/reset flip-flop or latch. The initial occlusion of an IR beam simultaneously sets a latch, delivers a locomotion pulse output, and resets any previously set latch whose IR beam is not occluded. A set latch causes its associated IR beam to be refractory to further locomotion movements until reset by the occlusion of a second IR beam. All beams are continuously responsive to stereotypic activity.

A new device to detect vocalizations by mice or rats is described. Of modest cost and incorporating integrated circuits and controls that permit rapid setting of center frequency and sensitivity, the device is based on phase-locked tone decoding and can operate at sonic or ultrasonic frequencies. Circuit operation and schematics are provided, as are data from two studies of mice in which reliable discrimination of distress and submission calls from background noise was demonstrated.