scholarly journals Prevalence of interfering antibodies in dogs and cats evaluated using a species-independent assay

2018 ◽  
Vol 47 (2) ◽  
pp. 205-212 ◽  
Author(s):  
Daniel Bergman ◽  
Anders Larsson ◽  
Helene Hansson-Hamlin ◽  
Anna Svensson ◽  
Bodil Ström Holst
Keyword(s):  
Independent Assay

4945Inclisiran-mediated reductions in Lp(a) in the ORION-1 trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R M Stoekenbroek ◽  
K K Ray ◽  
U Landmesser ◽  
L A Leiter ◽  
R S Wright ◽  
...  
Keyword(s):  
Ldl Receptor ◽  
Correlation Coefficients ◽  
Pcsk9 Inhibitors ◽  
Absolute Change ◽  
Phase 2 Trial ◽  
Spearman Coefficient ◽  
Ascvd Risk ◽  
Dose Dependent ◽  
Independent Assay

Abstract Background PCSK9 inhibitors and statins both lower LDL-C by increasing LDL-receptor (LDLR) function. PCSK9 inhibitors lower Lp(a) by 20–30%, whereas statins do not lower Lp(a). The mechanism by which PCSK9 inhibitors lower Lp(a) is unclear. We assessed the role of the LDLR in Lp(a) reductions produced by inclisiran, an siRNA which prevents hepatic synthesis of PCSK9. Methods ORION-1 was a phase 2 trial of inclisiran in subjects at high ASCVD risk with elevated LDL-C on optimized statin therapy. Subjects received one dose of inclisiran (200, 300, or 500 mg) or two doses at days 1 and 90 (100, 200, or 300 mg). We assessed the correlations between % change in Lp(a) and LDL-C at Day 180 for the inclisiran groups using Spearman correlation coefficients. We additionally assessed the correlation between % change in Lp(a) and absolute change in LDL-C as a proxy for LDLR expression. Lp(a) was measured using an isoform-independent assay and LDL-C with β-quantification. Results ORION-1 included 501 subjects; mean age 63; 65% male; 73% on statins. Median baseline Lp(a) was 37.0 nmol/l (IQR: 11.5–142.0 nmol/l), median LDL-C was 117.0 (IQR: 92.5–149.5 mg/dL). Inclisiran dose-dependently lowered Lp(a) by 14% to 26%. Overall, there was a significant but weak correlation between % change in Lp(a) LDL-C (Spearman coefficient 0.35, p<0.001). This correlation appeared to be stronger at higher inclisiran doses and with repeat dosing (table), as well as in statin-users versus non-users (Spearman coefficient 0.37 vs. 0.21). The correlation between % Lp(a) change and absolute LDL-C change was weaker (0.27, p<0.001). Correlation coefficients LDL-C – Lp(a) Single-dose groups Two-dose groups Inclisiran overall 200 mg (n=60) 300 mg (n=60) 500 mg (n=60) 100 mg (n=59) 200 mg (n=60) 300 mg (n=59) Lp(a) ∼ % change LDL-C 0.22 0.26 0.22 0.29 0.47 0.51 0.35 Lp(a) ∼ absolute change LDL-C 0.35 0.12 0.04 0.22 0.45 0.24 0.27 Lp(a) ∼ % change LDL-C - Statin users 0.16 0.28 0.28 0.31 0.45 0.55 0.37 Lp(a) ∼ % change LDL-C - Non statin users 0.80 -0.08 0.09 0.10 0.63 0.09 0.21 Conclusion The dose-dependent correlation between % changes in LDL-C and Lp(a) suggests that the LDLR may be partially responsible for Lp(a) reductions produced by inclisiran. The numerically stronger correlation in statin-users supports the idea that LDL-C may compete with Lp(a) for LDLR binding especially at low LDL-C levels. Acknowledgement/Funding The Medicines Company

scholarly journals Invasive Drosophila suzukii facilitates Drosophila melanogaster infestation and sour rot outbreaks in the vineyards

2017 ◽  
Vol 4 (3) ◽  
pp. 170117 ◽  
Author(s):  
A. Rombaut ◽  
R. Guilhot ◽  
A. Xuéreb ◽  
L. Benoit ◽  
M. P.  Chapuis ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Disease Outbreaks ◽  
Invasive Pest ◽  
Drosophila Suzukii ◽  
Extensive Disease ◽  
Field Collection ◽  
Invasive Pests ◽  
Sour Rot ◽  
Independent Assay ◽  
Grapevine Disease

How do invasive pests affect interactions between members of pre-existing agrosystems? The invasive pest Drosophila suzukii is suspected to be involved in the aetiology of sour rot, a grapevine disease that otherwise develops following Drosophila melanogaster infestation of wounded berries. We combined field observations with laboratory assays to disentangle the relative roles of both Drosophila in disease development. We observed the emergence of numerous D. suzukii , but no D. melanogaster flies, from bunches that started showing mild sour rot symptoms days after field collection. However, bunches that already showed severe rot symptoms in the field mostly contained D. melanogaster . In the laboratory, oviposition by D. suzukii triggered sour rot development. An independent assay showed the disease increased grape attractiveness to ovipositing D. melanogaster females. Our results suggest that in invaded vineyards, D. suzukii facilitates D. melanogaster infestation and, consequently, favours sour rot outbreaks. Rather than competing with close species, the invader subsequently permits their reproduction in otherwise non-accessible resources and may cause more frequent, or more extensive, disease outbreaks.

The mechanism of ryanodine action in rabbit ventricular muscle evaluated with Ca-selective microelectrodes and rapid cooling contractures

1987 ◽  
Vol 65 (4) ◽  
pp. 610-618 ◽  
Author(s):  
Donald M. Bers ◽  
John H. B. Bridge ◽  
Kenneth T. MacLeod
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Extracellular Space ◽  
Repetitive Stimulation ◽  
Ventricular Muscle ◽  
Half Time ◽  
Rapid Cooling ◽  
Ca Uptake ◽  
Rabbit Ventricular Muscle ◽  
Independent Assay ◽  
Cellular Ca

Cellular Ca uptake and efflux in rabbit ventricular muscle was measured using double-barreled Ca microelectrodes in the extracellular space. When repetitive stimulation was stopped there was a slow loss of cellular Ca. Upon resumption of stimulation Ca was taken up by the cells. These Ca movements are thought to represent the loss of Ca from the sarcoplasmic reticulum and the cell during rest and the refilling of the sarcoplasmic reticulum during stimulation. Ryanodine (100 nM) greatly enhanced both the efflux of Ca during rest and the uptake of Ca induced by stimulation. These results are consistent with the conclusions drawn below, but they are dependent upon the interpretation that these extracellular Ca depletions are indicative of sarcoplasmic reticulum Ca movements. To examine further this process, contractures induced by rapid cooling to 0 °C were used as an independent assay of sarcoplasmic reticulum Ca content. These rapid cooling contractures were smaller after longer rest intervals (declining with a half time of 1.5 min). In the presence of ryanodine, the rapid cooling contracture immediately after a contraction was greater than that seen under control conditions. However, in the presence of ryanodine these rapid cooling contractures decline as a function of rest duration with a half time of about 1 s. These results suggest that in the presence of ryanodine the sarcoplasmic reticulum can still take up Ca, but that it also loses this Ca very rapidly at the onset of rest. Caffeine (20 mM) inhibits both the extracellular Ca depletions and the rapid cooling contractures that are attributed to the sarcoplasmic reticulum Ca content changes (in the presence or absence of ryanodine). These results suggest the following two actions of ryanodine: (i) inhibition of sarcoplasmic reticulum Ca release into the cytoplasm upon activation, and (ii) enhancement of Ca loss from the sarcoplasmic reticulum upon the termination of stimulation and extrusion from the cell without activation of appreciable tension.

A pH-Independent Assay for Pectin Methyl Esterase for Use in Column Chromatography

1993 ◽  
Vol 209 (2) ◽  
pp. 377-379 ◽  
Author(s):  
G.P. Mcmillan ◽  
D.J. Johnston ◽  
J.B. Morel ◽  
M.C.M. Perombelon
Keyword(s):  
Column Chromatography ◽  
Pectin Methyl Esterase ◽  
Independent Assay

Quantification of phagocytosis of Aspergillus conidia by macrophages using a novel antibody-independent assay

2006 ◽  
Vol 66 (1) ◽  
pp. 170-173 ◽  
Author(s):  
Kathrin Luther ◽  
Manfred Rohde ◽  
Jürgen Heesemann ◽  
Frank Ebel
Keyword(s):  
Independent Assay

scholarly journals A simple trypsin resistance assay for muscle and other cell fusion.

1986 ◽  
Vol 34 (7) ◽  
pp. 959-962 ◽  
Author(s):  
G Denning ◽  
A B Fulton
Keyword(s):  
Gene Expression ◽  
Cell Fusion ◽  
Muscle Cells ◽  
Cell Loss ◽  
Lugol’S Iodine ◽  
Edta Solution ◽  
Specific Stage ◽  
Independent Assay ◽  
Study Development

Muscle cells fusing in vitro have long provided biologists with a tool to study development and gene expression. However, many such studies used morphological assays of cell fusion. We present here a method for assaying fusion at a specific, operationally defined step. Muscle cells grown in monolayer are exposed to trypsin-EDTA solution at 37 degrees C; the trypsin is inactivated, the cells fixed in Lugol's iodine, and 200 to 300 nuclei are counted as being single or multiple. The presence of EDTA is important under standard conditions for muscle culture; however, little difference is seen in divalent cation-depleted cultures. Therefore, for consistency EDTA can be included in all assays. Samples are stable for over 24 hr, with no cell loss from trypsinization or fixation. This assay exploits a specific stage of muscle fusion, trypsin-resistant contact, to provide a rapid, simple, and observer-independent assay for an early state of muscle fusion. The assay can be used to measure fusion between any nucleated cells.

scholarly journals Composition of Eukaryotic Viruses and Bacteriophages in Individuals with Acute Gastroenteritis

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2365
Author(s):  
Endrya do Socorro Fôro Ramos ◽  
Geovani de Oliveira Ribeiro ◽  
Fabiola Villanova ◽  
Flávio Augusto de Padua Milagres ◽  
Rafael Brustulin ◽  
...  
Keyword(s):  
Simultaneous Detection ◽  
Single Individual ◽  
Promising Tool ◽  
Northern Regions ◽  
Genomic Characterization ◽  
Human Viruses ◽  
Next Generation Sequencing Ngs ◽  
Viral Sequences ◽  
Independent Assay

Metagenomics based on the next-generation sequencing (NGS) technique is a target-independent assay that enables the simultaneous detection and genomic characterization of all viruses present in a sample. There is a limited amount of data about the virome of individuals with gastroenteritis (GI). In this study, the enteric virome of 250 individuals (92% were children under 5 years old) with GI living in the northeastern and northern regions of Brazil was characterized. Fecal samples were subjected to NGS, and the metagenomic analysis of virus-like particles (VLPs) identified 11 viral DNA families and 12 viral RNA families. As expected, the highest percentage of viral sequences detected were those commonly associated with GI, including rotavirus, adenovirus, norovirus (94.8%, 82% and 71.2%, respectively). The most common co-occurrences, in a single individual, were the combinations of rotavirus-adenovirus, rotavirus-norovirus, and norovirus-adenovirus (78%, 69%, and 62%, respectively). In the same way, common fecal-emerging human viruses were also detected, such as parechovirus, bocaporvirus, cosavirus, picobirnavirus, cardiovirus, salivirus, and Aichivirus. In addition, viruses that infect plants, nematodes, fungi, protists, animals, and arthropods could be identified. A large number of unclassified viral contigs were also identified. We show that the metagenomics approach is a powerful and promising tool for the detection and characterization of different viruses in clinical GI samples.

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