923 research outputs found

    Effectiveness of a Smoking Cessation Intervention for Methadone-Maintained Women: A Comparison of Pregnant and Parenting Women

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    Women in substance abuse programs have high rates of smoking. Pregnancy represents a unique opportunity for intervention, but few data exist to guide tailoring of effective interventions. In this study, 44 pregnant and 47 nonpregnant opioid-dependent women enrolled in comprehensive substance abuse treatment received a 6-week smoking cessation intervention based on the 5A's counseling model. The number of daily cigarettes decreased by 49% for pregnant patients and 32% for nonpregnant patients at the 3-month followup. Length of time in substance abuse treatment did not correlate with smoking cessation or reduction for either group. Factors predicting reduction of cigarette smoking differed for pregnant versus nonpregnant patients. For pregnant patients, lower levels of nicotine use prior to intervention and self-reported cigarette cravings predicted successful reduction in smoking. For nonpregnant patients, lower affiliative attachment to cigarettes, reliance on cigarettes for cognitive enhancement, and greater sense of control predicted more successful outcomes

    Functional Trade-Offs in Promiscuous Enzymes Cannot Be Explained by Intrinsic Mutational Robustness of the Native Activity.

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    The extent to which an emerging new function trades off with the original function is a key characteristic of the dynamics of enzyme evolution. Various cases of laboratory evolution have unveiled a characteristic trend; a large increase in a new, promiscuous activity is often accompanied by only a mild reduction of the native, original activity. A model that associates weak trade-offs with "evolvability" was put forward, which proposed that enzymes possess mutational robustness in the native activity and plasticity in promiscuous activities. This would enable the acquisition of a new function without compromising the original one, reducing the benefit of early gene duplication and therefore the selection pressure thereon. Yet, to date, no experimental study has examined this hypothesis directly. Here, we investigate the causes of weak trade-offs by systematically characterizing adaptive mutations that occurred in two cases of evolutionary transitions in enzyme function: (1) from phosphotriesterase to arylesterase, and (2) from atrazine chlorohydrolase to melamine deaminase. Mutational analyses in various genetic backgrounds revealed that, in contrast to the prevailing model, the native activity is less robust to mutations than the promiscuous activity. For example, in phosphotriesterase, the deleterious effect of individual mutations on the native phosphotriesterase activity is much larger than their positive effect on the promiscuous arylesterase activity. Our observations suggest a revision of the established model: weak trade-offs are not caused by an intrinsic robustness of the native activity and plasticity of the promiscuous activity. We propose that upon strong adaptive pressure for the new activity without selection against the original one, selected mutations will lead to the largest possible increases in the new function, but whether and to what extent they decrease the old function is irrelevant, creating a bias towards initially weak trade-offs and the emergence of generalist enzymes.This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC, Discovery Grant RGPIN 418262- 12, http://www.nserc-crsng.gc.ca/), the Biotechnology and Biological Sciences Research Council (BBSRC, Grant BB/L002469/1, http://www. bbsrc.ac.uk/), the European Research Council (ERC, Advanced Investigator Grant 695669, https:// erc.europa.eu/), and the Human Frontiers Science Program (Grant RGP0006/2013, http://www.hfsp. org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

    Skylab 4 visual observations project report

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    The Skylab 4 Visual Observations Project was undertaken to determine the ways in which man can contribute to future earth-orbital observational programs. The premission training consisted of 17 hours of lectures by scientists representing 16 disciplines and provided the crewmen information on observational and photographic procedures and the scientific significance of this information. During the Skylab 4 mission, more than 850 observations and 2000 photographs with the 70-millimeter Hasselblad and 35-millimeter Nikon cameras were obtained for many investigative areas. Preliminary results of the project indicate that man can obtain new and unique information to support satellite earth-survey programs because of his inherent capability to make selective observations, to integrate the information, and to record the data by describing and photographing the observational sites

    Philibaetis Gen. Nov., A New Genus from the Philippines (Ephemeroptera, Baetidae)

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    Investigations of type material and new material from the Philippines (Luzon) revealed that Baetis luzonensis Müller-Liebenau, 1982 and B. realonae Müller-Liebenau, 1982 do not belong to Baetis Leach, 1815. A new genus, Philibaetis gen. nov., is described to accommodate both species and both are re-described based on larvae. The new genus is characterised by having a rectangular labrum with a submarginal row of long, simple setae on the dorsal surface and ventrally on lateral margins long, simple, spine-like setae, on anterolateral margins long, feathered setae and medially long, bifid setae and a partial, submarginal row of lanceolate setae. Both mandibles have blade-like incisors and dorsally, a mediolateral patch of long, spine-like setae; additionally, the left mandible has a tuft of long, partly branched setae at the base of the subtriangular process. Philibaetis gen. nov. is further characterised by a hypopharynx with a medial tuft of stout setae and anterolaterally, two smaller tufts of stout setae, a galea-lacinia with the distal denti-seta tooth-like and directed against canines, a fore femur apically with stout setae, both on anterior and posterior side and without a femoral patch and a claw with one row of denticles and two or three subapical setae. The protogonostyli under the cuticle of male last instar larvae are folded in the Labiobaetis type, excluding their affiliation to the genus Baetis. COI sequences were obtained from both species. The genetic distance (Kimura 2-parameter) between them is 17.5% on average. Very limited genetic distances of 0% to 3% (0.75% on average) were found between specimens of P. luzonensis comb. nov

    First contribution to Labiobaetis Novikova & Kluge in Cambodia (Ephemeroptera, Baetidae), with description of two new species

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    Material collected in 2018 in Cambodia gives us first insights into the diversity of Labiobaetis Novikova & Kluge, 1987 in this country. No species has been reported so far. We identified two new species using a combination of morphology and genetic distance (COI, Kimura 2-parameter). They are described and illustrated based on their larvae. A key to all Labiobaetis species of continental Southeast Asia is provided. The interspecific K2P distance between the two new species is 20–21%, the intraspecific distance of one of them is 1%. The total number of Labiobaetis species worldwide is augmented to 156

    A new genus of Baetidae (Insecta, Ephemeroptera) from Southeast Asia

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    A new genus of Baetidae is described from Southeast Asia, Procerobaetis gen. nov. It has a wide distribution reaching from Indonesia (Sumatra) to the Philippines. Two new species are described from Indonesia, P. leptobranchius gen. et sp. nov. and P. petersorum gen. et sp. nov., and one new species from the Philippines, P. freitagi gen. et sp. nov. Procerobaetis gen. nov. is characterized by having seven pairs of elongate, apically pointed gills. At least gills I and II are very slender with strongly extended points, which is unique in Baetidae. Similar gills were described from Leptophlebiidae. Procerobaetis gen. nov. is further characterized by having long, slender legs with extended, slender and slightly bent claws. The antennae posess remarkable spines at the outer, lateral margin, which are maximally developed on segments IX–XI of the flagellum. No spines are present on the posterior margins of abdominal tergites I–VI. COI sequences were obtained from all three of the new species. The genetic distances (Kimura 2-parameter) between these species are between 13% and 20%. Very limited genetic distances of 0% to 1% were found between specimens of the same species. The occurrence of two different species in the same area of Sumatra is discussed

    Quasi-optimal Discontinuous Galerkin discretisations of the pp-Dirichlet problem

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    The classical arguments employed when obtaining error estimates of Finite Element (FE) discretisations of elliptic problems lead to more restrictive assumptions on the regularity of the exact solution when applied to non-conforming methods. The so-called minimal regularity estimates available in the literature relax some of these assumptions, but are not truly of -minimal regularity-, since a data oscillation term appears in the error estimate. Employing an approach based on a smoothing operator, we derive for the first time error estimates for Discontinuous Galerkin (DG) type discretisations of non-linear problems with (p,δ)(p,\delta)-structure that only assume the natural W1,pW^{1,p}-regularity of the exact solution, and which do not contain any oscillation terms

    Two new species of Centroptilum Eaton, 1869 from North Africa (Ephemeroptera, Baetidae).

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    Based on recently collected larvae from Algeria and Morocco, the species delimitation within the genus Centroptilum Eaton, 1869 in that region is validated. Two new species are described and illustrated, one from north-eastern Algeria, and one from North Morocco, using an integrated approach with morphological and molecular evidence. A table summarising the morphological differences between the new species and Centroptilumluteolum (Müller, 1776) from Central Europe is provided. Further, molecular evidence for additional undescribed species of Centroptilum in other regions of the West Palearctic is provided and discussed

    Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

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    Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications
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