224 research outputs found

    ASSESSING RIPARIAN ECOSYSTEM CONDITION AND MONITORING RECOVERY FROM NATURAL AND ANTHROPOGENIC DISTURBANCE

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    Riparian ecosystems are the transition zones between river systems and uplands. They provide many valuable ecological functions including creating habitat for wildlife, stabilizing banks from erosion and providing a buffer that prevents excess nutrients from entering streams. Fires and other disturbances alter the function of these ecosystems. Currently, there is a lack of broadly used standardized assessments and monitoring methods in riparian areas within our current water policy framework. This study aims to examine this gap in riparian ecosystem protection by reviewing the assessment methods currently in use, selecting one method for field testing, and analyzing the effort involved in using that method as a potential tool for the citizen science model to compare three riparian systems with different recovery times since last fire

    ¿Trasplantes incaicos o etnogénesis poscolonial? El origen de los salasacas de la Sierra ecuatoriana (Estudios)

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    The salasacas are an indigenous group with a controversial history of origen. Many manuscripts state that they descend from an uprooted Inca population that traveled north from present Bolivia to their new settlement that is now Ecuador. The article presents an alternative narrative that identifies three separate migrations to Salasaca, by different indigenas groups, in the Sixteenth Century. It shows that the modern Salasacan nationality emerged during colonial and postcolonial transformations. It contends that the ethnic distinction of the salasacas is due to the fact that they opted to collectively unite as one solid ethnic group in order to remain as an Indigenas enclave in a region that was experiencing whitening or widespread emergence of half castes.Los salasacas son un grupo indígena con una historia de origen controversial. Muchos escritos declaran que descienden de una población trasplantada por los incas desde la actual Bolivia hasta su ubicación en lo que hoy es Ecuador. El artículo presenta una narrativa alternativa que identifica tres migraciones a Salasaca, de diferentes grupos indígenas, en el siglo XVI. Se demuestra que la nacionalidad moderna de Salasaca surgió a través de transformaciones coloniales y poscoloniales. Se argumenta que la distinción étnica de los salasacas se debe a que optaron por unificarse como un solo grupo étnico para permanecer como enclave indígena en una región que experimentó el blanqueamiento cultural o mestizaje

    Antibody-Drug Nanoparticle Induces Synergistic Treatment Efficacies in HER2 Positive Breast Cancer Cells

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    Chemotherapeutic drugs suffer from non-specific binding, undesired toxicity, and poor blood circulation which contribute to poor therapeutic efficacy. In this study, antibody–drug nanoparticles (ADNs) are engineered by synthesizing pure anti-cancer drug nanorods (NRs) in the core of nanoparticles with a therapeutic monoclonal antibody, Trastuzumab on the surface of NRs for specific targeting and synergistic treatments of human epidermal growth factor receptor 2 (HER2) positive breast cancer cells. ADNs were designed by first synthesizing ~ 95 nm diameter × ~ 500 nm long paclitaxel (PTX) NRs using the nanoprecipitation method. The surface of PTXNRs was functionalized at 2′ OH nucleophilic site using carbonyldiimidazole and conjugated to TTZ through the lysine residue interaction forming PTXNR-TTZ conjugates (ADNs). The size, shape, and surface charge of ADNs were characterized using scanning electron microscopy (SEM), SEM, and zeta potential, respectively. Using fluorophore labeling and response surface analysis, the percentage conjugation efficiency was found \u3e 95% with a PTX to TTZ mass ratio of 4 (molar ratio ≈ 682). In vitro therapeutic efficiency of PTXNR-TTZ was evaluated in two HER2 positive breast cancer cell lines: BT-474 and SK-BR-3, and a HER2 negative MDA-MB-231 breast cancer cell using MTT assay. PTXNR-TTZ inhibited \u3e 80% of BT-474 and SK-BR-3 cells at a higher efficiency than individual PTX and TTZ treatments alone after 72 h. A combination index analysis indicated a synergistic combination of PTXNR-TTZ compared with the doses of single-drug treatment. Relatively lower cytotoxicity was observed in MCF-10A human breast epithelial cell control. The molecular mechanisms of PTXNR-TTZ were investigated using cell cycle and Western blot analyses. The cell cycle analysis showed PTXNR-TTZ arrested \u3e 80% of BT-474 breast cancer cells in the G2/M phase, while \u3e 70% of untreated cells were found in the G0/G1 phase indicating that G2/M arrest induced apoptosis. A similar percentage of G2/M arrested cells was found to induce caspase-dependent apoptosis in PTXNR-TTZ treated BT-474 cells as revealed using Western blot analysis. PTXNR-TTZ treated BT-474 cells showed ~ 1.3, 1.4, and 1.6-fold higher expressions of cleaved caspase-9, cytochrome C, and cleaved caspase-3, respectively than untreated cells, indicating up-regulation of caspase-dependent activation of apoptotic pathways. The PTXNR-TTZ ADN represents a novel nanoparticle design that holds promise for targeted and efficient anti-cancer therapy by selective targeting and cancer cell death via apoptosis and mitotic cell cycle arrest

    Reducing Poverty in California…Permanently

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    If California were to seriously commit to equalizing opportunity and reducing poverty, how might that commitment best be realized? This is of course a hypothetical question, as there is no evidence that California is poised to make such a serious commitment, nor have many other states gone much beyond the usual lip-service proclamations. There are many reasons for California’s complacency, but an important one is that most people think that poverty is intractable and that viable solutions to it simply don’t exist. When Californians know what needs to be done, they tend to go forward and get it done. When, for example, the state’s roads are in disrepair, there are rarely paralyzing debates about exactly how to go about fixing them; instead we proceed with the needed repairs as soon as the funds to do so are appropriated. The same type of sure and certain prescription might appear to be unavailable when it comes to reducing poverty. It is hard not to be overwhelmed by the cacophony of voices yielding a thick stream of narrow-gauge interventions, new evaluations, and piecemeal proposals.1 Although the research literature on poverty is indeed large and may seem confusing, recent advances have in fact been so fundamental that it is now possible to develop a science-based response to poverty. In the past, the causes of poverty were not well understood, and major interventions, such as the War on Poverty, had to be built more on hunch than science. It is an altogether different matter now. The causes of poverty are well established, and the effects of many possible policy responses to poverty are likewise well established. The simple purpose of this essay is to assemble these advances into a coherent plan that would, if implemented, reduce poverty in California substantially

    Energetic, structural, and antimicrobial analyses of β-lactam side chain recognition by β-lactamases

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    AbstractBackground: Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these β-lactams, most often through bacterial expression of β-lactamases, threatens public health. To understand how β-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because β-lactams form covalent adducts with β-lactamases. This has complicated functional analyses and inhibitor design.Results: To investigate the contribution to interaction energy of the key amide (R1) side chain of β-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well as four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine β-lactamases. Therefore, binding energies can be calculated directly from Ki values. The Ki values measured span four orders of magnitude against the Group I β-lactamase AmpC and three orders of magnitude against the Group II β-lactamase TEM-1. The acylglycineboronic acids have Ki values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of β-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of β-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to β-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 Å and 1.75 Å resolution; these structures suggest interactions that are important to the affinity of the inhibitors.Conclusions: Acylglycineboronic acids allow us to begin to dissect interaction energies between β-lactam side chains and β-lactamases. Surprisingly, there is little correlation between the affinity contributed by R1 side chains and their occurrence in β-lactam inhibitors or β-lactam substrates of serine β-lactamases. Nevertheless, presented in acylglycineboronic acids, these side chains can lead to inhibitors with high affinities and specificities. The structures of their complexes with AmpC give a molecular context to their affinities and may guide the design of anti-resistance compounds in this series

    Developing an implementation fidelity checklist for a vocational rehabilitation intervention

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    Background: Despite growing numbers of studies reporting the efficacy of complex interventions and their implementation, many studies fail to report information on implementation fidelity or describe how fidelity measures used within the study were developed. This study aimed to develop a fidelity checklist for measuring the implementation fidelity of an early, stroke-specialist vocational rehabilitation intervention (ESSVR) in the RETAKE trial. Methods: To develop the fidelity measure, previous checklists were reviewed to inform the assessment structure, and core intervention components were extracted from intervention descriptions into a checklist, which was ratified by eight experts in fidelity measurement and complex interventions. Guidance notes were generated to assist with checklist completion. To test the measure, two researchers independently applied the checklist to fifteen stroke survivor intervention case notes using retrospective observational case review. The scoring was assessed for interrater reliability. Results: A fidelity checklist containing 21 core components and 6 desirable components across 4 stages of intervention delivery was developed with corresponding guidance notes. Interrater reliability of each checklist item ranged from moderate to perfect (Cohen’s kappa 0.69–1). Conclusions: The resulting checklist to assess implementation fidelity is fit for assessing the delivery of vocational rehabilitation for stroke survivors using retrospective observational case review. The checklist proved its utility as a measure of fidelity and may be used to inform the design of future implementation strategies.publishedVersio

    18S-NemaBase: Curated 18S rRNA Database of Nematode Sequences

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    Nematodes are the most abundant and diverse animals on the planet but lack representation in biodiversity research. This presents a problem for studying nematode diversity, particularly when molecular tools (i.e., barcoding and metabarcoding) rely on well-populated and curated reference databases, which are absent for nematodes. To improve molecular identification and the assessment of nematode diversity, we created and curated an 18S rRNA database specific to nematodes (18S-NemaBase) using sequences sourced from the most recent publicly available 18S rRNA SILVA v138 database. As part of the curation process, taxonomic strings were standardized to contain a fixed number of taxonomic ranks relevant to nematology and updated for the most recent accepted nematode classifications. In addition, apparent erroneous sequences were removed. To test the efficacy and accuracy of 18S-NemaBase, we compared it to an older but also curated SILVA v111 and the newest SILVA v138 by assigning taxonomies and analyzing the diversity of a nematode dataset from the Western Nebraska Sandhills. We showed that 18S-NemaBase provided more accurate taxonomic assignments and diversity assessments than either version of SILVA, with a much easier workflow and no need for manual corrections. Additionally, observed diversity further improved when 18S-NemaBase was supplemented with reference sequences from nematodes present in the study site. Although the 18S-NemaBase is a step in the right direction, a concerted effort to increase the number of high-quality, accessible, full-length nematode reference sequences is more important now than ever
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