GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Material
Language
  • 1
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 9, No. 26 ( 2023-06-30)
    Abstract: The identification of asymmetric protection between Zika and Spondweni viruses in macaques suggests a model for future study.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 2810933-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    Online Resource
    Online Resource
    Institute of Electrical and Electronics Engineers (IEEE) ; 2019
    In:  IEEE Transactions on Image Processing Vol. 28, No. 9 ( 2019-9), p. 4471-4485
    In: IEEE Transactions on Image Processing, Institute of Electrical and Electronics Engineers (IEEE), Vol. 28, No. 9 ( 2019-9), p. 4471-4485
    Type of Medium: Online Resource
    ISSN: 1057-7149 , 1941-0042
    Language: Unknown
    Publisher: Institute of Electrical and Electronics Engineers (IEEE)
    Publication Date: 2019
    detail.hit.zdb_id: 2034319-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Kansas Agricultural Experiment Station Research Reports, New Prairie Press, Vol. 8, No. 10 ( 2022-01-01)
    Type of Medium: Online Resource
    ISSN: 2378-5977
    Language: English
    Publisher: New Prairie Press
    Publication Date: 2022
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 6_suppl ( 2013-02-20), p. 135-135
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 135-135
    Abstract: 135 Background: We have previously reported a phase I/II trial with a DNA vaccine encoding PAP in patients with stage M0 CaP. Vaccination was found to be safe and immunologically active. Th1-biased PAP-specific immune responses were associated with increases in PSA doubling time (DT). In the current trial, we sought to evaluate the immunological efficacy of immunizations performed over a 1-2-year period of time, with the goal of identifying a preferred schedule. Methods: Patients (pts) were randomized to a schedule of 6 immunizations at 2-wk intervals followed by quarterly booster immunizations, or a schedule determined by frequent immune monitoring. Immune monitoring was by IFNγ and granzyme B ELISPOT and antigen-specific T-cell proliferation. Pts continued immunization until evidence of radiographic progression, toxicity, two years, or 24 total immunizations, whichever occurred first. Results: 17 pts were enrolled, of whom 11 completed at least 1 year on treatment, and 4 completed 2 years. 3 pts remain on study. 1 pt experienced a grade 3 allergic reaction (angioedema) after 11 immunizations; no other events 〉 grade 2 were observed. 6/16 evaluable pts developed durable immune responses, defined as statistically significant PAP-specific T-cell responses by at least two separate measures that were at least 3-fold the baseline response and detectable at 〉 1 post-treatment time point. 2 pts in the immune-monitoring arm developed immune responses after 6 immunizations that were detectable at each quarterly time point up to 2 years. 5/15 evaluable pts were observed to have a 〉 3-fold increase in PSA DT; the 2 with the greatest increase in PSA DT developed PAP-specific IFNγ-secreting T cells detectable at multiple time points after immunization. Conclusions: Repetitive immunization with this vaccine appears safe and immunologically active. Presence of durable Th1-biased antigen-specific immune responses is a mechanistically rational biomarker, and may be associated with favorable increases in PSA DT observed in 2 separate trials. Impact of vaccination on time to radiographic disease progression awaits results from an ongoing randomized clinical trial. Clinical trial information: NCT00849121.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    In: mBio, American Society for Microbiology, Vol. 13, No. 3 ( 2022-06-28)
    Abstract: The main protease, M pro , of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here, we report quantitative reporters for M pro function in living cells in which protease inhibition by genetic or chemical methods results in robust signal readouts by fluorescence (enhanced green fluorescent protein [eGFP]) or bioluminescence (firefly luciferase). These gain-of-signal systems are scalable to high-throughput platforms for quantitative discrimination between M pro mutants and/or inhibitor potencies as evidenced by validation of several reported inhibitors. Additional utility is shown by single M pro amino acid variants and structural information combining to demonstrate that both inhibitor conformational dynamics and amino acid differences are able to influence inhibitor potency. We further show that a recent variant of concern (Omicron) has an unchanged response to a clinically approved drug, nirmatrelvir, whereas proteases from divergent coronavirus species show differential susceptibility. Together, we demonstrate that these gain-of-signal systems serve as robust, facile, and scalable assays for live cell quantification of M pro inhibition, which will help expedite the development of next-generation antivirals and enable the rapid testing of emerging variants. IMPORTANCE The main protease, M pro , of SARS-CoV-2 is an essential viral protein required for the earliest steps of infection. It is therefore an attractive target for antiviral drug development. Here, we report the development and implementation of two complementary cell-based systems for quantification of M pro inhibition by genetic or chemical approaches. The first is fluorescence based (eGFP), and the second is luminescence based (firefly luciferase). Importantly, both systems rely upon gain-of-signal readouts such that stronger inhibitors yield higher fluorescent or luminescent signal. The high versatility and utility of these systems are demonstrated by characterizing M pro mutants and natural variants, including Omicron, as well as a panel of existing inhibitors. These systems rapidly, safely, and sensitively identify M pro variants with altered susceptibilities to inhibition, triage-nonspecific, or off-target molecules and validate bona fide inhibitors, with the most potent thus far being the first-in-class drug nirmatrelvir.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2557172-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2017
    In:  Scientific Reports Vol. 7, No. 1 ( 2017-12-05)
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-12-05)
    Abstract: HIV-1 replication requires myriad interactions between cellular proteins and the viral unspliced RNA. These interactions are important in archetypal RNA processes such as transcription and translation as well as for more specialized functions including alternative splicing and packaging of unspliced genomic RNA into virions. We present here a hybridization capture strategy for purification of unspliced full-length HIV RNA-protein complexes preserved in vivo by formaldehyde crosslinking, and coupled with mass spectrometry to identify HIV RNA-protein interactors in HIV-1 infected cells. One hundred eighty-nine proteins were identified to interact with unspliced HIV RNA including Rev and Gag/Gag-Pol, 24 host proteins previously shown to bind segments of HIV RNA, and over 90 proteins previously shown to impact HIV replication. Further analysis using siRNA knockdown techniques against several of these proteins revealed significant changes to HIV expression. These results demonstrate the utility of the approach for the discovery of host proteins involved in HIV replication. Additionally, because this strategy only requires availability of 30 nucleotides of the HIV-RNA for hybridization with a capture oligonucleotide, it is readily applicable to any HIV system of interest regardless of cell type, HIV-1 virus strain, or experimental perturbation.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    In: Journal of Virology, American Society for Microbiology, Vol. 96, No. 1 ( 2022-01-12)
    Abstract: HIV-1 virion production is driven by Gag and Gag-Pol (GP) proteins, with Gag forming the bulk of the capsid and driving budding, while GP binds Gag to deliver the essential virion enzymes protease, reverse transcriptase, and integrase. Virion GP levels are traditionally thought to reflect the relative abundances of GP and Gag in cells (∼1:20), dictated by the frequency of a −1 programmed ribosomal frameshifting (PRF) event occurring in gag-pol mRNAs. Here, we exploited a panel of PRF mutant viruses to show that mechanisms in addition to PRF regulate GP incorporation into virions. First, we show that GP is enriched ∼3-fold in virions relative to cells, with viral infectivity being better maintained at subphysiological levels of GP than when GP levels are too high. Second, we report that GP is more efficiently incorporated into virions when Gag and GP are synthesized in cis (i.e., from the same gag-pol mRNA) than in trans , suggesting that Gag/GP translation and assembly are spatially coupled processes. Third, we show that, surprisingly, virions exhibit a strong upper limit to trans -delivered GP incorporation; an adaptation that appears to allow the virus to temper defects to GP/Gag cleavage that may negatively impact reverse transcription. Taking these results together, we propose a “weighted Goldilocks” scenario for HIV-1 GP incorporation, wherein combined mechanisms of GP enrichment and exclusion buffer virion infectivity over a broad range of local GP concentrations. These results provide new insights into the HIV-1 virion assembly pathway relevant to the anticipated efficacy of PRF-targeted antiviral strategies. IMPORTANCE HIV-1 infectivity requires incorporation of the Gag-Pol (GP) precursor polyprotein into virions during the process of virus particle assembly. Mechanisms dictating GP incorporation into assembling virions are poorly defined, with GP levels in virions traditionally thought to solely reflect relative levels of Gag and GP expressed in cells, dictated by the frequency of a −1 programmed ribosomal frameshifting (PRF) event that occurs in gag-pol mRNAs. Herein, we provide experimental support for a “weighted Goldilocks” scenario for GP incorporation, wherein the virus exploits both random and nonrandom mechanisms to buffer infectivity over a wide range of GP expression levels. These mechanistic data are relevant to ongoing efforts to develop antiviral strategies targeting PRF frequency and/or HIV-1 virion maturation.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1495529-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    In: Translational Animal Science, Oxford University Press (OUP), Vol. 7, No. 1 ( 2023-01-01)
    Abstract: A total of 320 pigs (Line 241 × 600, DNA, Columbus, NE; initially 11.9 ± 0.22 kg) were used in a 21-d growth study to determine the available P (aP) release curve for Smizyme TS G5 2,500 (Barentz, Woodbury, MN). At approximately 19 d of age, pigs were weaned, randomly allotted to pens, and fed common starter diets. Pigs were blocked by average pen body weight (BW) and randomly allotted to one of eight dietary treatments on day 18 postweaning, considered day 0 of the study. Dietary treatments were derived from a single basal diet and ingredients including phytase, monocalcium P, limestone, and sand were added to create the treatment diets. Treatments included three diets containing increasing inorganic P from monocalcium P (0.11%, 0.20%, and 0.28% aP), or five diets with increasing phytase (500, 1,000, 1,500, 2,000, or 2,500 FTU/kg) added to the diet containing 0.11% aP. All diets were corn–soybean meal–canola meal-based and were formulated to contain 1.24% standardized ileal digestibility Lys, 0.30% phytate P, and an analyzed Ca:P ratio of 1.10:1. Prior to the beginning of the study, all pigs were fed a diet containing 0.11% aP for a 2-d period (days 16 to 18 postweaning). At the conclusion of the study, one pig, closest to the mean weight of each pen, was euthanized and the right fibula, rib, and metacarpal were collected to determine bone ash, density, and total bone P. Bones were weighed while suspended in a vessel of water and the weights used to calculate bone density (Archimedes’ principle). For bone ash, bones were processed using the non-defatted method. For the overall experimental period, pigs fed increasing inorganic P had increased (quadratic, P ≤ 0.033) average daily gain (ADG), average daily feed intake (ADFI), and final BW and a tendency for increased (quadratic, P ≤ 0.090) gain:feed ratio (G:F). Pigs fed increasing phytase had increased (quadratic, P ≤ 0.004) ADG, G:F, and final BW and increased (linear, P = 0.019) ADFI. For fibula, rib, and metacarpal characteristics, pigs fed increasing aP from inorganic P had increased (linear, P  & lt; 0.001) bone ash weight, percentage bone ash, bone density, and bone P concentration. Additionally, pigs fed increasing phytase had increased (linear or quadratic, P  & lt; 0.05) bone ash weight, percentage bone ash, bone density, and bone P. TheaP release curve generated for Smizyme TS G5 2,500 for percentage bone ash using data generated from all three bones is aP = (0.228 × FTU/kg) ÷ (998.065 + FTU/kg).
    Type of Medium: Online Resource
    ISSN: 2573-2102
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2880940-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Journal of Animal Science Vol. 100, No. Supplement_2 ( 2022-04-12), p. 18-18
    In: Journal of Animal Science, Oxford University Press (OUP), Vol. 100, No. Supplement_2 ( 2022-04-12), p. 18-18
    Abstract: A total of 360 pigs (Line 200 × 400, DNA, Columbus, NE, initially 9.9 ± 0.19 kg) were used in a 21-d growth study to determine the available P (aP) release curve for GraINzyme phytase (Agrivida Inc., Woburn, MA). Pigs were weaned at approximately 21-d of age, randomly allotted to pens based on initial body weight (BW) and fed common starter diets. From d 18 to 21 post-weaning, all pigs were fed a diet containing 0.11% aP. On d 21 post-weaning, considered d 0 of the study, pens were blocked by BW and randomly allotted to 1 of 8 dietary treatments with 5 pigs/pen and 9 pens/treatment. Dietary treatments were formulated to include increasing aP derived from either an inorganic P source (0.11, 0.19, or 0.27% from monocalcium P) or increasing phytase (150, 250, 500, 1,000, or 1,500 FTU/kg). Diets were corn-soybean meal-based and contained 1.24% standardized ileal digestible (SID) Lys. On d 21 of the trial, 1 pig/pen (weighing closest to the mean pen BW) was euthanized and the right fibula was collected to determine bone ash using the non-defatted processing method. Overall (d 0 to 21), pigs fed increasing aP from inorganic P or phytase had increased (linear, P & lt; 0.002) ADG, ADFI, and G:F (quadratic, P & lt; 0.05). Bone ash weight (g) and percentage bone ash increased (linear, P & lt; 0.001) with increasing inorganic P or added phytase. The release equations developed for GraINzyme for ADG, G:F, bone ash weight, and percentage bone ash are: aP = (0.255 × FTU) ÷ (1,299.969 + FTU), aP = (0.233 × FTU) ÷ (1,236.428 + FTU), aP = (45,999.949 × FTU) ÷ (462,529,200 + FTU), and aP = (0.272 × FTU) ÷ (2,576.581 + FTU), respectively.
    Type of Medium: Online Resource
    ISSN: 0021-8812 , 1525-3163
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1490550-4
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2020
    In:  Pediatric Rheumatology Vol. 18, No. 1 ( 2020-12)
    In: Pediatric Rheumatology, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2020-12)
    Abstract: Inflammatory arthritis in children with Down syndrome (DS) was first described in 1984 and is now termed Down syndrome-associated arthritis (DA). Studies have shown that DA is under-recognized with a 19-month average delay in diagnosis. Additionally, most patients present with polyarticular, rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative disease. Current therapies for juvenile idiopathic arthritis (JIA) have been used, but appear to be poorly tolerated, more toxic and less effective in patients with DA. There is currently no standardized approach to the assessment or management of DA. The objective of this study was to describe provider perspectives toward diagnostic and treatment approach of DA, to provide baseline information upon which to design future studies. Methods An electronic survey, organized into sections regarding individual practices of assessment and treatment approach of DA, was sent to the Pediatric Rheumatology electronic list-serv. Survey responses were voluntary and results were analyzed by descriptive statistics. Results Of 90 survey responses received, 89 were included in the analysis (one was a duplicate response). The respondents were mostly pediatric rheumatologist (94%), with greater than 10 years of experience (55%). The majority (64%) currently see 1–3 patients with DA. Most view DA as the same disease as JIA (73%), and the majority (63%) use a combination of history, exam and imaging to diagnose DA. The most ordered diagnostic tests are CBC (97%) and ESR (96%). The most used treatments include NSAIDs (94%) and methotrexate (91%) followed by anti-TNF agents (90%). Methotrexate is most administered by subcutaneous route (84%) at a dose of 15 mg/m 2 (56%). Oral corticosteroids were only used in 19% of the patients with DA. Conclusion This is the first study to evaluate provider perspectives towards the diagnostic and treatment approach of DA. Most pediatric rheumatologists feel that DA and JIA are synonymous, and similar approaches to diagnosis are employed, utilizing history, physical exam, laboratory tests, and imaging modalities. DA is treated similarly to JIA with initiation of NSAIDs, disease-modifying anti-rheumatic drugs and biologic therapy. More research is needed to determine optimal screening and therapeutic approach specific to DA.
    Type of Medium: Online Resource
    ISSN: 1546-0096
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2279468-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...