1,724,550 research outputs found
ABBV-4083 treatment clears microfilaremia and inhibits filarial embryogenesis.
No full textA, Microfilariae counts over time in L. sigmodontis infected jirds that were treated for 14 days with ABBV-4083 (1x 100mg/kg per day, n = 6), doxycycline (DOX, 2x 40mg/kg per day, 14 days, n = 6) or (1x VEH per day, n = 6) starting at 12 wpi. Data are presented as mean + SEM. B, embryograms from female adult worms isolated from L. sigmodontis infected jirds treated orally either with ABBV-4083 (1x 100mg/kg per day, 7 or 14 days, n = 6 jirds), doxycycline (DOX, 2x 40mg/kg per day, 14 days, n = 6 jirds) or vehicle (VEH, n = 6 jirds) at the time of necropsy 1, 4, 14 wpt (VEH = 10 worms; DOX = 20 worms; ABBV-4083 1wpt = 25 worms; ABBV-4083 4wpt = 20 worms; ABBV-4083 14wpt = 25 worms). The following embryonic stages were counted: egg, morula, pretzel and stretched microfilaria (MF). Data are presented as median.</p
Continuous daily treatments with ABBV-4083 are not required for depletion of <i>Wolbachia</i> and microfilariae.
No full textA, experimental design. L. sigmodontis-infected jirds were treated orally either with ABBV-4083 1x 25mg/kg (mpk) QD consecutively for 7, 10 or 14 days (n = 6–7, consecutively (Con) treated group), or discontinuously (Dis) for 7 days total with skipped treatments on days 6 and 8 or discontinuously for 14 days with skipped treatments on days 6, 8, 13, and 15 (n = 6). Vehicle treated animals served as negative controls (VEH, n = 7), ABBV-4083 1x 50mg/kg for 14 day treated animals served as positive control. B, Wolbachia ftsZ/act ratio of isolated female adult worms at 8 weeks after treatment start (VEH = 12 worms; ABBV-4083 50mg/kg Con = 16 worms; ABBV-4083 25mg/kg 7d Con = 23 worms; ABBV-4083 25mg/kg 7d Dis = 9 worms; ABBV-4083 25mg/kg 10d Con = 19 worms; ABBV-4083 25mg/kg 14d Con = 27 worms; ABBV-4083 25mg/kg 14d Dis = 13 worms). Data were tested for normality by d‘Agostino & Pearson test. Statistical significance of not normally distributed data shown in B was analyzed by Kruskal-Wallis followed by Dunn’s multiple comparison test. ***pWolbachia ftsZ/microfilaria over time (mean + SEM). D, Spearman correlation of Wolbachia ftsZ/microfilariae and median ftsZ/female adult worms from the same animals at 8wpt. E, Microfilariae counts over time (mean + SEM) and F, embryograms from female adult worms (VEH = 6 worms; ABBV-4083 50mg/kg Con = 6 worms; ABBV-4083 25mg/kg 7d Con = 10 worms; ABBV-4083 25mg/kg 7d Dis = 1 worm; ABBV-4083 25mg/kg 10d Con = 7 worms; ABBV-4083 25mg/kg 14d Con = 16 worms; ABBV-4083 25mg/kg 14d Dis = 8 worms). The following embryonic stages were counted: egg, morula, pretzel and stretched MF, as well as degenerated early (egg, morula) and late (pretzel, stretched MF) stages. Data are presented as median.</p
Linked collectors and determiners for: Allocybaeina littlewalteri (Araneae: Cybaeidae): a new genus and species endemic to northwestern California.
No full textNatural history specimen data linked to collectors and determiners held within, "Allocybaeina littlewalteri (Araneae: Cybaeidae): a new genus and species endemic to northwestern California". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/4a1fd7f9-9585-4083-8588-2592be2f41e0">https://bionomia.net/dataset/4a1fd7f9-9585-4083-8588-2592be2f41e0</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/4a1fd7f9-9585-4083-8588-2592be2f41e0">https://gbif.org/dataset/4a1fd7f9-9585-4083-8588-2592be2f41e0</a>. Formatted as a Frictionless Data package
<i>Wolbachia</i> decline during and after ABBV-4083 treatment with twice daily treatment showing no significant superiority over once daily treatment.
No full textA, experimental design. 8-week-old female mice (n = 5–8 mice/group) were infected naturally with L. sigmodontis. At 35dpi the animals were treated orally either with ABBV-4083 (1x (QD) or 2x (BID) 75mg/kg (mpk) per day) for 3, 5, 7 or 10 days with necropsies at 38, 40, 42, 45 & 63dpi or doxycycline (DOX, 2x 40mg/kg per day) for 10 days and necropsy at 63dpi. Controls received an equal amount of vehicle (VEH, necropsy 38, 40, 42, 45 or 63dpi). B, Wolbachia ftsZ/act per female adult worm was quantified by real-time PCR (38dpi: VEH 3d = 60 worms; ABBV-4083 QD 3d = 36 worms; 40dpi: VEH 3d = 57 worms; ABBV-4083 QD 5d = 52 worms; ABBV-4083 BID 5d = 59 worms; 42dpi: VEH 7d = 59 worms; ABBV-4083 QD 7d = 52 worms; 45dpi: VEH 10d = 51 worms; ABBV-4083 QD 10d = 41 worms; 63dpi: VEH 5d = 43 worms; ABBV-4083 QD 5d = 37 worms; ABBV-4083 BID 5d = 60 worms; ABBV-4083 QD 10d = 47 worms, DOX BID 10d = 48 worms). C, experimental design. 8- to 10-week-old female mice (n = 5 mice/group) were infected naturally with L. sigmodontis and treated orally with ABBV-4083 (1x 43mg/kg; 2x 43mg/kg; 1x 50mg/kg; 1x 75mg/kg per day) or VEH for 5 days starting 36dpi with necropsies at 41dpi. D, Wolbachia ftsZ/act per female worm (VEH 5d = 37 worms; ABBV-4083 43mg/kg QD 5d = 27 worms; ABBV-4083 43mg/kg BID 5d = 19 worms; ABBV-4083 50mg/kg QD 5d = 26 worms; ABBV-4083 75mg/kg QD 5d = 17 worms). Data were tested for normal distribution by d‘Agostino & Pearson test. Statistical significance of not normally distributed data (B, D) was analyzed by Kruskal-Wallis followed by Dunn’s multiple comparison test. The horizontal lines indicate the median. p*<0.05, **p<0.01, ***p<0.001, compared with VEH.</p
Spatial interpolation of age appropriate vaccination practice in Ethiopia using EDHS 2016(n = 4083).
No full textSpatial interpolation of age appropriate vaccination practice in Ethiopia using EDHS 2016(n = 4083).</p
Defective interaction between Pol2p and Dpb2p, subunits of DNA polymerase epsilon, contributes to a mutator phenotype in Saccharomyces cerevisiae.
Full text linkMost of the prokaryotic and eukaryotic replicative polymerases are multi-subunit complexes. There are several examples indicating that noncatalytic subunits of DNA polymerases may function as fidelity factors during replication process. In this work, we have further investigated the role of Dpb2p, a noncatalytic subunit of DNA polymerase epsilon holoenzyme from Saccharomyces cerevisiae in controlling the level of spontaneous mutagenesis. The data presented indicate that impaired interaction between catalytic Pol2p subunit and Dpb2p is responsible for the observed mutator phenotype in S. cerevisiae strains carrying different mutated alleles of the DPB2 gene. We observed a significant correlation between the decreased level of interaction between different mutated forms of Dpb2p towards a wild-type form of Pol2p and the strength of mutator phenotype that they confer. We propose that structural integrity of the Pol epsilon holoenzyme is essential for genetic stability in S. cerevisiae cells
Spatial distribution of age appropriate vaccination practice in Ethiopia using EDHS -2016 (n = 4083).
No full textSpatial distribution of age appropriate vaccination practice in Ethiopia using EDHS -2016 (n = 4083).</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
In vivo kinetics of Wolbachia depletion by ABBV-4083 in L. sigmodontis adult worms and microfilariae.
Full text linkDepletion of Wolbachia endosymbionts of human pathogenic filariae using 4-6 weeks of doxycycline treatment can lead to permanent sterilization and adult filarial death. We investigated the anti-Wolbachia drug candidate ABBV-4083 in the Litomosoides sigmodontis rodent model to determine Wolbachia depletion kinetics with different regimens. Wolbachia reduction occurred in mice as early as 3 days after the initiation of ABBV-4083 treatment and continued throughout a 10-day treatment period. Importantly, Wolbachia levels continued to decline after a 5-day-treatment from 91.5% to 99.9% during a 3-week washout period. In jirds, two weeks of ABBV-4083 treatment (100mg/kg once-per-day) caused a >99.9% Wolbachia depletion in female adult worms, and the kinetics of Wolbachia depletion were recapitulated in peripheral blood microfilariae. Similar to Wolbachia depletion, inhibition of embryogenesis was time-dependent in ABBV-4083-treated jirds, leading to a complete lack of late embryonic stages (stretched microfilariae) and lack of peripheral microfilariae in 5/6 ABBV-4083-treated jirds by 14 weeks after treatment. Twice daily treatment in comparison to once daily treatment with ABBV-4083 did not significantly improve Wolbachia depletion. Moreover, up to 4 nonconsecutive daily treatments within a 14-dose regimen did not significantly erode Wolbachia depletion. Within the limitations of an animal model that does not fully recapitulate human filarial disease, our studies suggest that Wolbachia depletion should be assessed clinically no earlier than 3-4 weeks after the end of treatment, and that Wolbachia depletion in microfilariae may be a viable surrogate marker for the depletion within adult worms. Furthermore, strict daily adherence to the dosing regimen with anti-Wolbachia candidates may not be required, provided that the full regimen is subsequently completed
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