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961.
Govindan Subramanian Scott J. Bowen Yaqi Zhu Nicole Roush Theresa Zachary Christopher Javens Tracey Williams Ann Janssen Andrea Gonzales 《Bioorganic & medicinal chemistry letters》2019,29(19):126624
In silico virtual screening using the ligand-based ROCS approach and the commercially purchasable compound collection from the ZINC database resulted in the identification of distinctly different and novel acetamide core frameworks with series representatives 1a and 2a exhibiting nanomolar affinity in the kinase domain only hTrkA HTRF biochemical assay. Additional experimental validation using the Caliper technology with either the active or inactive kinase conditions demonstrated the leads, 1a and 2a, to preferentially bind the kinase inactive state. X-ray structural analysis of the kinase domain of hTrkA…1a/2a complexes confirmed the kinase, bind the inhibitor leads in the inactive state and to exhibit a type 2 binding mode with the DFG-out and αC-helix out conformation. The leads also demonstrated sub-micromolar activity in the full length hTrkA cell-based assay and selectivity against the closely related hTrkB isoform. However, the poor microsomal stability and permeability of the leads is suggestive of a multiparametric lead optimization effort requirement for further progression. 相似文献
962.
Calorimetry and other on-line techniques are used for the first time as complement to the traditional off-line methods in order to follow the growth of the green Chlorella vulgaris microalgae. A 2-L photo-bio-reactor was adapted from a commercial calorimeter used previously to study heterotrophic microbial growth. An external source of light was added to favor the photosynthesis of the autotrophic cells. Heterotrophic growth was also tested with external glucose in the broth. A third mode, mixotrophic, allowed faster autotrophic plus heterotrophic growth. Calorimetric measurements were performed considering the corresponding calibrations in order to consider only the energy involved during the microalgal growth. The three different modes of Chlorella cultures were energetically characterized. Besides calorimetry, the weight of diluted nitric acid added to maintain the pH of the culture was correlated with the cellular growth and the nitrogen composition of the algae. Additionally, the on-line infrared spectroscopy proved to be an efficient technique to follow the composition of the broth in glucose, nitrates, and phosphates. These results were compared and complemented with some classic off-line techniques used to track this kind of cultures. 相似文献
963.
Calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians 总被引:1,自引:0,他引:1
Vollmert C Hahn S Lamina C Huth C Kolz M Schöpfer-Wendels A Mann K Bongardt F Mueller JC Kronenberg F Wichmann HE Herder C Holle R Löwel H Illig T Janssen OE;KORA group 《American journal of physiology. Endocrinology and metabolism》2007,292(3):E836-E844
PCOS is known to be associated with an increased risk of T2DM and has been proposed to share a common genetic background with T2DM. Recent studies suggest that the Calpain-10 gene (CAPN10) is an interesting candidate gene for PCOS susceptibility. However, contradictory results were reported concerning the contribution of certain CAPN10 variants, especially of UCSNP-44, to genetic predisposition to T2DM, hirsutism, and PCOS. By means of MALDI-TOF MS technique, we genotyped an expanded single nucleotide polymorphism panel, including the CAPN10 UCSNP-44, -43, -56, ins/del-19, -110, -58, -63, and -22 in a sample of 146 German PCOS women and 606 population-based controls. Statistical analysis revealed an association between UCSNP-56 and susceptibility to PCOS with an odds ratio (OR) of 2.91 (95% CI=1.51-5.61) for women carrying an AA genotype compared with GG. As expected, the 22-genotype of the ins/del-19 variant, which is in high linkage disequilibrium (r2=0.98) with UCSNP-56, was also significantly associated (OR=2.98, 95% CI=1.55-5.73). None of the additionally tested variants alone showed any significant association with PCOS. A meta-analysis including our study (altogether 623 PCOS cases and 1,224 controls) also showed significant association only with ins/del-19. The most common haplotype TGG3AGCA was significantly associated with a lower risk for PCOS (OR=0.487, P=0.0057). In contrast, the TGA2AGCA haplotype was associated with an increased risk for PCOS (OR=3.557, P=0.0011). By investigating a broad panel of CAPN10 variants, our results pointed to an allele dose-dependent association of UCSNP-56 and ins/del-19 with PCOS. 相似文献
964.
Endogenous circadian clocks are inherent to all living organisms. They are needed to guarantee successful life since they regulate very important biological processes such as behavior and reproduction. Secretin-like G-protein coupled receptors are very important factors in the signal transduction pathways of circadian clocks. In this review, we will focus on the role of two secretin-like signaling pathways that play an important role in the regulation of the mammalian and the insect clock, respectively: the pituitary adenylate cyclase-activating polypeptide (PACAP) and pigment dispersing factor (PDF) signaling pathways. Both pathways are most likely related although their function in the biological clock differs. 相似文献
965.
Hiranandani N Raman S Kalyanasundaram A Periasamy M Janssen PM 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(1):R30-R36
One of the prominent markers of end-stage heart failure at the molecular level is a decrease in function and/or expression of the sarcoplasmic reticulum ATPase protein [sarco(endo)plasmic reticulum calcium-ATPase, SERCA]. It has been often postulated that a decrease in SERCA pump activity can contribute in a major way to decreased cardiac function. To establish a functional relationship, we assessed how alterations in SERCA activity level affect basic contractile function in healthy myocardium devoid of other significant molecular changes. We investigated baseline contractile function, frequency-dependent activation, and beta-adrenergic response in ultrathin trabeculae isolated from hearts of mice overexpressing SERCA (transgenic, TG), underexpressing SERCA2a (heterozygous knockout, Het), and their respective wild-type (WT) littermates. At physiological temperature and frequency, compared with their respective WT littermates, SERCA1a mice displayed increased developed force at frequencies of 4-8 Hz ( approximately 90% increase at 4 Hz) and force equal to WT mice at 10-14 Hz. Force development at 4 Hz in presence of 1 muM isoproterenol was similar in TG and WT mice. In Het mice, developed force was nearly identical at the lower end of the frequency range (4-8 Hz) but slightly depressed at higher frequency (P < 0.05 at 14 Hz). In presence of 1 muM isoproterenol, developed force at 4 Hz was equal to that in WT mice. Compared with normal levels, increased SERCA activity enhanced force development only at subphysiological frequencies. A reduction in SERCA activity only showed a depression of force at the higher frequency range. Thus generalizations regarding the correlation between SERCA activity and contractility can be highly ambiguous, because this relationship is critically dependent on other factors including stimulation frequency. 相似文献
966.
Janssen M Geeraerd AH Cappuyns A Garcia-Gonzalez L Schockaert G Van Houteghem N Vereecken KM Debevere J Devlieghere F Van Impe JF 《Applied and environmental microbiology》2007,73(5):1601-1611
In food technology, organic acids (e.g., lactic acid, acetic acid, and citric acid) are popular preservatives. The purpose of this study was to separate the individual effects of the influencing factors pH and undissociated lactic acid on Listeria innocua inactivation. Therefore, the inactivation process was investigated under controlled, initial conditions of pH (pH0) and undissociated lactic acid ([LaH]0). The resulting inactivation curves consisted of a (sometimes negligible) shoulder period followed by a descent phase. In a few cases, a tailing phase was observed. Depending on the conditions, the descent phase contained one or two log-linear parts or had a convex or concave shape. In addition, the inactivation process was characterized by a certain variability, dependent on the severity of the conditions. Furthermore, in the neighborhood of the growth/no growth interface sometimes contradictory observations occurred. Overall, the individual effects of the influencing factors pH and undissociated lactic acid could clearly be distinguished and were also apparent based on fluorescence microscopy. Appropriate model types were developed and enabled prediction of which conditions of pH0 and [LaH]0 are necessary to obtain a predetermined inactivation (number of decimal reductions) within a predetermined time range. 相似文献
967.
Lima Andressa Oliveira Malheiros Jessica Moraes Afonso Juliana Petrini Juliana Coutinho Luiz Lehmann da Silva Diniz Wellison Jarles Bressani Flávia Aline Tizioto Polyana Cristine de Oliveira Priscila Silva Neubern Ribeiro Janssen Ayna Silva de Oliveira Karina Santos Rocha Marina Ibelli Pereira Andrade Bruno Gabriel Nascimento Fukumasu Heidge Beiki Hamid Reecy James Mark Zerlotini Adhemar Mourao Gerson Barreto de Almeida Regitano Luciana Correia 《Mammalian genome》2022,33(4):629-641
Mammalian Genome - Animal feeding is a critical factor in increasing producer profitability. Improving feed efficiency can help reduce feeding costs and reduce the environmental impact of beef... 相似文献
968.
It is well known that herbivore-induced plant defenses alter host plant quality and can affect the behavior and performance of later arriving herbivores.Effects of sequential attacks by herbivores that either suppress or induce plant defenses are less well studied.We sequentially infested leaves of tomato plants with a strain of the phytophagous spider mite Tetranychus urticae that induces plant defenses and the closely related Tetranychus evansi, which suppresses plant defenses.Plant quality was quantified through oviposifion of both spider mite species and by measuring proteinase inhibitor activity using plant material that had been sequentially attacked by both herbivore species.Spider-mite oviposifion data show that T.evansi could suppress an earlier induction of plant defenses by T.urticae,and T.urticae could induce defenses in plants previously attacked by T.evansi in 1 day.Longer attacks by the second species did not result in further changes in oviposifion.Proteinase inhibitor activity levels showed that T.evansi suppressed the high activity levels induced by T.urticae to constitutive levels in 1 day,and further suppressed activity to levels similar to those in plants attacked by T.evansi alone.Attacks by T.urticae induced proteinase inhibitor activity in plants previously attacked by T.evansi,eventually to similar levels as induced by T.urticae alone.Hence,plant quality and plant defenses were significantly affected by sequential attacks and the order of attack does not affect subsequent performance,but does affect proteinase inhibitor activity levels.Based on our results,we discuss the evolution of suppression of plant defenses. 相似文献
969.