1,723,615 research outputs found
PPAR-delta Agonist MBX-8025 Abolishes Lipotoxicity andReverses NASH in Diabetic Obese Mice
No full textBackground: Lipotoxicity associated with insulin resistance
and diabetes is central to the pathogenesis of non-alcoholic
steatohepatitis (NASH), and resultant liver fibrosis and
cirrhosis. To date, only weight loss, which improves insulin
sensitivity, reverses NASH fibrosis; pharmacological agents
have limited efficacy. The mixed peroxisome proliferator-activated
receptor-alpha/delta (PPAR-α/δ) agonist, GFT505, has
demonstrated some efficacy in NASH. MBX-8025 is a selective
PPAR-δ agonist that improves atherogenic dyslipidemia
in rodents and humans. We tested whether MBX-8025 could
reverse lipotoxicity and NASH in a diabetic mouse model.
Methods: From 4 weeks of age, female Alms1 mutant (foz/
foz) and wildtype (Wt) mice were fed an atherogenic diet for
16 weeks, after which groups (8-12 mice) were randomized
to receive MBX-8025 (10mg/kg) or vehicle (1% methylcellulose)
by gavage for 8 weeks. We performed intraperitoneal
glucose tolerance testing (IpGTT) at Week 27, and sacrifice at
28 weeks. Results: MBX-8025 had minimal effect on body or
liver weight, but normalized hyperglycemia, hypercholesterolaemia,
hyperinsulinemia and glucose disposal (by IpGTT) in
foz/foz mice. After 16 weeks of atherogenic dietary intake,
serum ALT ranged from 300-600 U/L in vehicle-treated foz/
foz mice; MBX-8025 reduced this by ~50% (P<0.05). In foz/
foz mice, hepatic lipid fractions showed increased free cholesterol,
diacylglycerol, saturated fatty acid and triglyceride
content. MBX-8025 normalized serum lipids, and corrected
all hepatic lipid pools. This was associated with abolition of
hepatocyte ballooning, substantial reduction of steatosis, and
reduced liver inflammation with a striking decrease in the number
of macrophage crown-like structures; the resultant non-alcoholic
fatty liver disease (NAFLD) Activity Score (NAS) was 6.9
(range 6-7) indicated all vehicle-treated foz/foz mice (8/8)
showed definite NASH. MBX-8025 reversed NASH in all foz/
foz mice (NAS 3.13; P<0.05), with only residual simple steatosis
being present. MBX-8025 also repressed development of
liver fibrosis, quantified by collagen densitometry and mRNA
analyses. Conclusions: The selective PPAR-δ agonist MBX-8025
improves glucose tolerance and reverses diabetes, atherogenic
dyslipidemia, hepatic lipid storage (including lipotoxic lipids),
and NASH pathology in atherogenic diet-fed diabetic mice.
MBX-8025 acts independently of weight reduction, appears to
counter lipotoxicity related to insulin resistance, with accompanying
reductions in liver inflammation and fibrosis. MBX-8025
provides a novel mechanism-based therapeutic agent to treat
NASH
Linked collectors and determiners for: Review of the genera Agelosus Sharp, 1889, Apostenolinus Bernhauer, 1934 and Apecholinus Bernhauer, 1933 (Coleoptera: Staphylinidae: Staphylinini: Staphylinina).
No full textNatural history specimen data linked to collectors and determiners held within, "Review of the genera Agelosus Sharp, 1889, Apostenolinus Bernhauer, 1934 and Apecholinus Bernhauer, 1933 (Coleoptera: Staphylinidae: Staphylinini: Staphylinina)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/bb5c58a5-3a4a-4c8b-8025-7e71e77c2782">https://bionomia.net/dataset/bb5c58a5-3a4a-4c8b-8025-7e71e77c2782</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/bb5c58a5-3a4a-4c8b-8025-7e71e77c2782">https://gbif.org/dataset/bb5c58a5-3a4a-4c8b-8025-7e71e77c2782</a>. Formatted as a Frictionless Data package
Digitalisierung (6): R 8025 Baltische Landeswehr
No full textBArch, R 8025/11, fol.8 (Ausschnitt) Im November 1918, nach dem Waffenstillstand von Compiègne, wurde die Baltische Landeswehr in Riga zur Verteidigung des Landes gegen die von Osten vordringenden bolschewistischen Truppen gegründet. Sie bestand hauptsächlich aus Formationen der Deutschbalten, aber auch aus kleineren lettischen und russischen Abteilungen. Zusammen mit den Freikorps wurde sie im Februar 1919 dem Oberkommando des Generals Rüdiger Graf von der Goltz unterstellt. Der Stoßtrupp ..
Atherosclerosis Effects of the PPAR-␦ agonist MBX-8025 on atherogenic dyslipidemia
No full texta b s t r a c t Objective: Determine the effects of treatment with a selective PPAR-␦ agonist ± statin on plasma lipoprotein subfractions in dyslipidemic individuals. Methods: Ion mobility analysis was used to measure plasma concentrations of subfractions of the full spectrum of lipoprotein particles in 166 overweight or obese dyslipidemic individuals treated with the PPAR-␦ agonist MBX-8025 (50 and 100 mg/d) ± atorvastatin (20 mg/d) in an 8-week randomized parallel arm double blind placebo controlled trial. Results: MBX-8025 at both doses resulted in reductions of small plus very small LDL particles and increased levels of large LDL, with a concomitant reduction in large VLDL, and an increase in LDL peak diameter. This translated to reversal of the small dense LDL phenotype (LDL pattern B) in ∼90% of the participants. Modest increases in HDL particles were confined to the smaller HDL fractions. Atorvastatin monotherapy resulted in reductions in particles across the VLDL-IDL-LDL spectrum, with a significantly smaller reduction in small and very small LDL vs. MBX-8025 100 mg/d (−24.5 ± 5.3% vs. −47.8 ± 4.9%), and, in combination with MBX-8025, a reversal of the increase in large LDL. Conclusion: PPAR-␦ and statin therapies have complementary effects in improving lipoprotein subfractions associated with atherogenic dyslipidemia
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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Socio-demographic and obstetric characteristics of women delivered at KCMC in subsequent pregnancy, 2000–2018 (N = 8025).
No full textSocio-demographic and obstetric characteristics of women delivered at KCMC in subsequent pregnancy, 2000–2018 (N = 8025).</p
Distribution of pre-term, term, and post-term by year among women delivered at KCMC in 2000–2018 (N = 8025).
No full textDistribution of pre-term, term, and post-term by year among women delivered at KCMC in 2000–2018 (N = 8025).</p
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