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71.
Beshay N. Zordoky Miranda M. Sung Justin Ezekowitz Rupasri Mandal Beomsoo Han Trent C. Bjorndahl Souhaila Bouatra Todd Anderson Gavin Y. Oudit David S. Wishart Jason R. B. Dyck Alberta HEART 《PloS one》2015,10(5)
BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is increasingly recognized as an important clinical entity. Preclinical studies have shown differences in the pathophysiology between HFpEF and HF with reduced ejection fraction (HFrEF). Therefore, we hypothesized that a systematic metabolomic analysis would reveal a novel metabolomic fingerprint of HFpEF that will help understand its pathophysiology and assist in establishing new biomarkers for its diagnosis.ConclusionsThe metabolomics approach employed in this study identified a unique metabolomic fingerprint of HFpEF that is distinct from that of HFrEF. This metabolomic fingerprint has been utilized to identify two novel panels of metabolites that can separate HFpEF patients from both non-HF controls and HFrEF patients.
Clinical Trial Registration
ClinicalTrials.gov NCT02052804相似文献72.
Siamak Ravanbakhsh Philip Liu Trent C. Bjordahl Rupasri Mandal Jason R. Grant Michael Wilson Roman Eisner Igor Sinelnikov Xiaoyu Hu Claudio Luchinat Russell Greiner David S. Wishart 《PloS one》2015,10(5)
Many diseases cause significant changes to the concentrations of small molecules (a.k.a. metabolites) that appear in a person’s biofluids, which means such diseases can often be readily detected from a person’s “metabolic profile"—i.e., the list of concentrations of those metabolites. This information can be extracted from a biofluids Nuclear Magnetic Resonance (NMR) spectrum. However, due to its complexity, NMR spectral profiling has remained manual, resulting in slow, expensive and error-prone procedures that have hindered clinical and industrial adoption of metabolomics via NMR. This paper presents a system, BAYESIL, which can quickly, accurately, and autonomously produce a person’s metabolic profile. Given a 1D 1H
NMR spectrum of a complex biofluid (specifically serum or cerebrospinal fluid), BAYESIL can automatically determine the metabolic profile. This requires first performing several spectral processing steps, then matching the resulting spectrum against a reference compound library, which contains the “signatures” of each relevant metabolite. BAYESIL views spectral matching as an inference problem within a probabilistic graphical model that rapidly approximates the most probable metabolic profile. Our extensive studies on a diverse set of complex mixtures including real biological samples (serum and CSF), defined mixtures and realistic computer generated spectra; involving > 50 compounds, show that BAYESIL can autonomously find the concentration of NMR-detectable metabolites accurately (~ 90% correct identification and ~ 10% quantification error), in less than 5 minutes on a single CPU. These results demonstrate that BAYESIL is the first fully-automatic publicly-accessible system that provides quantitative NMR spectral profiling effectively—with an accuracy on these biofluids that meets or exceeds the performance of trained experts. We anticipate this tool will usher in high-throughput metabolomics and enable a wealth of new applications of NMR in clinical settings. BAYESIL is accessible at http://www.bayesil.ca. 相似文献
73.
Harsha L. Rao Viquar U. Begum Deepa Khadka Anil K. Mandal Sirisha Senthil Chandra S. Garudadri 《PloS one》2015,10(5)
PurposeTo compare the rate of mean deviation (MD) change on 24-2 versus 10-2 VFs in treated glaucomatous eyes with 5 or more examinations.MethodsIn a retrospective study, 24-2 and 10-2 VFs of 131 glaucoma patients (167 eyes) who had undergone at least 5 VFs examinations during their follow-up were analyzed. All these patients had VF defects both on 24-2 and 10-2 VFs. Rates of MD change were calculated using best linear unbiased predictions (BLUP).ResultsMedian age, MD on 24-2 VF at baseline, number of VFs performed during follow-up and follow-up duration were 55 years, -16.9 dB, 9 and 9 years respectively. Median rate of MD change was significantly greater (p<0.001) on 10-2 VF (-0.26 dB/year; interquartile range [IQR]: -0.47, -0.11) compared to 24-2 VFs (-0.19 dB/year; IQR: -0.41, -0.03). Comparing the rates of MD change in eyes with different severities of VF loss (early [MD better than -6 dB], moderate [-6 dB to -12 dB], advanced [-12 to -20 dB] and severe [MD worse than -20 dB]) at baseline (based on the MD on 24-2 VF), median rate of MD change was comparable between 10-2 and 24-2 VFs in mild (-0.45 dB/year vs. -0.40 dB/year, P = 0.42) and moderate (-0.32 dB/year vs. -0.40 dB/year, P = 0.26) VF loss categories, while the same were significantly greater on 10-2 VFs in advanced (-0.28 dB/year vs. -0.21 dB/year, P = 0.04) and severe (-0.18 dB/year vs. -0.06 dB/year, P<0.001) VF loss categories.ConclusionsIn patients with VF defects both on 24-2 and 10-2 VFs, evaluating the rate of MD change on 10-2 VFs may help in better estimation of glaucoma progression, especially so in eyes with advanced glaucoma at baseline. 相似文献
74.
Saptarshi Roy G. Aditya Kumar Md. Jafurulla Chitra Mandal Amitabha Chattopadhyay 《生物化学与生物物理学报:生物膜》2014
Visceral leishmaniasis is a vector-borne disease caused by an obligate intracellular protozoan parasite Leishmania donovani. The molecular mechanism involved in internalization of Leishmania is poorly understood. The entry of Leishmania involves interaction with the plasma membrane of host cells. We have previously demonstrated the requirement of host membrane cholesterol in the binding and internalization of L. donovani into macrophages. In the present work, we explored the role of the host actin cytoskeleton in leishmanial infection. We observed a dose-dependent reduction in the attachment of Leishmania promastigotes to host macrophages upon destabilization of the actin cytoskeleton by cytochalasin D. This is accompanied by a concomitant reduction in the intracellular amastigote load. We utilized a recently developed high resolution microscopy-based method to quantitate cellular F-actin content upon treatment with cytochalasin D. A striking feature of our results is that binding of Leishmania promastigotes and intracellular amastigote load show close correlation with cellular F-actin level. Importantly, the binding of Escherichia coli remained invariant upon actin destabilization of host cells, thereby implying specific involvement of the actin cytoskeleton in Leishmania infection. To the best of our knowledge, these novel results constitute the first comprehensive demonstration on the specific role of the host actin cytoskeleton in Leishmania infection. Our results could be significant in developing future therapeutic strategies to tackle leishmaniasis. 相似文献
75.
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77.
Inocula were collected from four different sources such as Jajmau tannery waste treatment plant (ITW), Jajmau municipal waste treatment (IMW), Unnao distillery (IDW) and a batch reactor, in which the sludge of a field scale biogas reactor was added to cow dung slurry to develop inoculum (IBS). A combination of these mixed inocula were used for biogas production at 35°C in laboratory scale reactor (10 L capacity) and the average yield of biogas (0.547 Lg?1 volatile solid (VS)) and methane (0.323 Lg?1VS) in 41 d was higher in case of mixed inoculum IMW 1 (IMW+IBS), with maximum methane content in biogas (68% during 27–30 d), as compared to other mixed inocula as well as control i.e. ITW 1 (ITW+IBS), IDW1 (IDW+IBS) and IBS. The corresponding yields of gas were biogas (0.505, 0.536 and 0.456 Lg?1VS), methane (0.288, 0.305, and 0.245 Lg?1VS) where as, the corresponding maximum methane content in biogas was 62% during 29–33d, 64% during 29–33 d and 62% during 27–29 d in ITW1, IDW1 and IBS. 相似文献
78.
Downy mildew (Peronospora plantaginis) caused two different types of infection in the floral parts of isabgol (Plantago ovata). Systemic infection resulted in long spikes bearing weak and sterile florets, which later turned black due to saprophytic
growth. Localised infection produced various symptoms ranging between normal flower opening and failure to bloom. Different
parts of infected flowers such as sepal, petal, filament and anther were reduced in size compared to healthy flowers. However,
gynoecium was elongated in localised infection. P. plantaginis induced gradual sterility of isabgol flowers. Androecium was affected more than the gynoecium was. Pollen number, pollen
viability and germination reduced drastically due to localised infection. On the contrary, there were no significant differences
between healthy and locally infected flowers in terms of stigma receptivity. In systemically infected spikes, bud development
was arrested leading to sterility. When localised disease severity was high, secondary systemic infection caused similar symptoms.
Microscopic observations showed presence of the pathogen in different parts of the flowers. Downy mildew adversely affected
seed yield and quality; producing seeds, which were smaller and lighter than the healthy ones and later, became black. Seed
yield was reduced by as much as 73.45 percent. Husk content per unit seed mass increased relatively as the total surface area
of infected seeds increased. 相似文献
79.
Yan-Feng Li Wei He Young-Hwan Kim Arabinda Mandal Laura Digilio Ken Klotz Charles J Flickinger John C Herr 《Reproductive biology and endocrinology : RB&E》2010,8(1):101
Background
CABYR is a polymorphic calcium-binding protein of the sperm fibrous sheath (FS) which gene contains two coding regions (CR-A and CR-B) and is tyrosine as well as serine/threonine phosphorylated during in vitro sperm capacitation. Thus far, the detailed information on CABYR protein expression in mouse spermatogenesis is lacking. Moreover, because of the complexity of this polymorphic protein, there are no data on how CABYR isoforms associate and assemble into the FS. 相似文献80.
Katherine E. Smith Gary Fooks Jeff Collin Heide Weishaar Sema Mandal Anna B. Gilmore 《PLoS medicine》2010,7(1)