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Bisphenol A (BPA) is a chemical used in the production of certain plastics and resins. Recent research has found that BPA can inhibit the activity of 3β-hydroxysteroid dehydrogenase/Δ5,4-isomerases (3β-HSDs). Whether benzene ring BPA substitutes can inhibit human, rat, and mouse gonadal 3β-HSDs, the structure-activity relationship and the underlying mechanism remain unclear. In this study, we compared 6 benzene ring BPA substitutes to BPA in the inhibition of human, rat, and mouse gonadal 3β-HSDs and conducted structure-activity relationship and in silico docking analysis. The inhibitory activity (IC 50) of human 3β-HSD2 in KGN cells ranged from about 0.02 μM for bisphenol H to 8.75 μM for BPA, that of rat 3β-HSD1 in testicular microsomes ranged from 0.099 μM for bisphenol H to 31.32 μM for BPA, and that of mouse 3β-HSD6 ranged from 0.021 μM for BPH to ineffectiveness for 100 μM BPA. These compounds acted as mixed inhibitors with LogP inversely correlated with IC 50 and ΔG positively correlated with IC 50 value. Docking analysis showed that these compounds bind to the steroid active site of the 3β-HSD enzymes. In conclusion, some benzene ring BPA substitutes potently inhibit gonadal 3β-HSD in various species, and lipophilicity and binding affinity determine their inhibitory strength. [Display omitted] • Benzene ring BPA derivatives potent inhibit human, rat, and mouse gonadal 3β-HSD. • BPH is the most potent inhibitor of human 3β-HSD2. • BPH is ineffective to inhibit rat and mouse gonadal 3β-HSD. • Benzene ring significantly increases the inhibitory potency of BPA derivatives. [ABSTRACT FROM AUTHOR]

The mechanisms underlying neuroinflammation following cerebral ischemia remain unclear. Hydrogen sulfide (H 2 S), a newly identified gasotransmitter, has been reported to regulate inflammation. In the current study, we investigated whether the endogenous H 2 S production pathway contributed to microglia-mediated neuroinflammation following stroke. We used a mouse middle cerebral artery occlusion (MCAO) model and an in vitro cellular model to mimic ischemia-induced microglial neuroinflammation. Expression of the H 2 S synthase cystathionine β-synthase (CBS) and H 2 S synthetic activity were rapidly decreased in the ischemic brain tissue following MCAO. Consistently, when cultured microglia were polarized toward a pro-inflammatory phenotype with conditioned medium collected from neurons that had been subjected to oxygen-glucose deprivation (OGD neuron CM), they displayed reduced CBS expression and H 2 S production. Enhancing H 2 S bioavailability either by overexpressing CBS or by supplementing with exogenous H 2 S donors promoted a shift in microglial polarization from ischemia-induced pro-inflammatory phenotypes toward anti-inflammatory phenotypes. Mechanistically, microglia that were exposed to OGD neuron CM displayed reduced activation of AMP-activated protein kinase (AMPK), which was rescued by overexpressing CBS or by supplementing with H 2 S donors. Moreover, the promoting effects of H 2 S donors on microglial anti-inflammatory polarization were abolished by an AMPK inhibitor or CaMKKβ inhibitor. Our results suggested that reduced CBS-H 2 S-AMPK cascade activity contributed to microglia-mediated neuroinflammation following stroke. Targeting the CBS-H 2 S pathway is a promising therapeutic approach for ischemic stroke. [ABSTRACT FROM AUTHOR]

Coordination for dynamic task allocation based on available resources is a very challenging research issue in disaster environments with time, space and communication constraints. In addition, the space and communication constraints and the dynamic features of disaster environments make an extra difficulty to achieve efficient coordination through centralised coordination approaches, which require the coordinators to have global knowledge of the environments. To this end, a coordination approach for dynamic weighted task allocation is proposed in this paper. The proposed approach considers time, space and communication constraints in disaster environments and urgent degrees of workloads of tasks without requiring the global knowledge of the environment. In particular, a dynamic group formation mechanism is developed to help agents to form groups and share information for task allocation under space and communication constraints in a decentralised manner, which can reflect real-life situations in disaster environments. The efficient coordination for task allocation is achieved through the utility calculation within each group. The experimental results show that the proposed approach outperforms most of other coordination approaches, such as the group formation approach proposed by Glinton et al. and the heuristics task allocation approach proposed by Ramchurn et al. in terms of group formation and weighted task allocation in disaster environments with time, space and communication constraints. [ABSTRACT FROM AUTHOR]

The energy dispatch problem is a fundamental research issue in power distribution networks. With the growing complexity and dimensions of current distribution networks, there is an increasing need for intelligent and scalable mechanisms to facilitate energy dispatch in these networks. To this end, in this paper, we propose a multi-agent coalition formation-based energy dispatch mechanism. This mechanism is decentralised without requiring a central controller or any global information. As this mechanism does not need a central controller, the single point of failure can be avoided and since this mechanism does not require any global information, good scalability can be expected. In addition, this mechanism enables each node in a distribution network to make decisions autonomously about energy dispatch through a negotiation protocol. Simulation results demonstrate the effectiveness of this mechanism in comparison with three recently developed representative mechanisms. [ABSTRACT FROM AUTHOR]

Let F q be the finite field of order q and let M m × n (F q) be the additive (abelian) group consisting of all m × n matrices over F q. Given an integer r with 0 ≤ r ≤ min ⁡ { m , n } , the Cayley graph G (m , n , r) is defined as the graph whose vertices are consisting of all the elements of M m × n (F q) , and two vertices A , B ∈ M m × n (F q) are adjacent if the rank of A − B (denoted by r a n k (A − B)) is equal to r. In this paper, a recursion relation for the eigenvalues of G (m , n , r) is established; consequently, explicit formulas for all the eigenvalues of G (m , n , 1) are exhibited immediately, which is a main result obtained previously in Delsarte (1975) [4]. [ABSTRACT FROM AUTHOR]

The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair. [ABSTRACT FROM AUTHOR]

Abstract: In service-oriented computing applications, service consumers and providers need to evaluate the trust levels of potential partners before engaging in interactions. The accuracy of trust evaluation greatly affects the success rate of the interaction. Trust evaluation is a challenging problem in open and dynamic environment as there is no central mediator to manage standardized evaluation criteria or reputation records. In this paper, a novel trust model, called the priority-based trust model, is presented. The model derives the trustworthiness of a service provider from designated referees and its historical performance. In addition, consumers can specify their preferred priorities which will affect the result of trust evaluations. The experimental results show that the proposed model has better performance than other trust models, especially in open and dynamic environments. [Copyright &y& Elsevier]

• Decrease data amount largely by introducing an electric mixer. • Compare 4 classifiers on basis of a large set of data of 5 sound events. • Point out an ELM classifier with RBF kernel is optimal in φ-OTDR systems. We investigate two kinds of event detection methods, support vector machine (SVM) and extreme learning machine (ELM), for distributed acoustic sensors (DAS) using phase-sensitive optical time domain reflectometer (φ-OTDR). We propose a heterodyne coherent φ-OTDR platform using an electric mixer, select spectrogram image feature (SIF) as a feature vector, and make comparison of the performance of 4 event classifiers. Theoretical and experimental analysis point out that an ELM classifier with RBF kernel is optimal in the detection of 5 sound events that has high identification accuracy, less training time, less testing time and strong noise immunity, which promises to be the first choice of event detection method in φ-OTDR systems in industrial applications. [ABSTRACT FROM AUTHOR]

There is an intimate connection between mitochondrial DNA (mtDNA) methylation and some diseases, such as cancer. MtDNA is almost strictly maternally inherited. However, whether the aberrant mtDNA methylation involved in breast cancer progression and whether mtDNA methylation can be transmitted through maternal line are poorly understood. Here we applied bisulfite sequencing to global mitochondrial DNA and whole genomic DNA methylation array from fifteen members of five three-female-generation families with one breast cancer patient in each family. We found that mtDNA methylation was maternally inherited in D-loop region and eight aberrant mtDNA methylation sites were correlated with breast cancer. Furthermore, conjoint analysis showed that mtDNA methylation sites could be potential biomarkers combined with nuclear DNA methylation sites for breast cancer risk prediction. [ABSTRACT FROM AUTHOR]

Mitophagy is the selective degradation of mitochondria by autophagy, which is an important mitochondrial quality and quantity control process. During Drosophila metamorphosis, the degradation of midgut involves a large change in length and organization, which is mediated by autophagy. Here we noticed a cell-type specific mitochondrial clearance process that occurs in enterocytes (ECs), while most mitochondria remain in intestinal stem cells (ISCs) during metamorphosis. Although PINK1/PARKIN represent the canonical pathway for the elimination of impaired mitochondria in varied pathological conditions, their roles in developmental processes or normal physiological conditions have been less studied. To examine the potential contribution of PINK1 in developmental processes, we monitored the dynamic expression pattern of PINK1 in the midgut development by taking advantage of a newly CRISPR/Cas9 generated knock-in fly strain expressing PINK1-mCherry fusion protein that presumably recapitulates the endogenous expression pattern of PINK1. We disclosed a spatiotemporal correlation between the expression pattern of PINK1 and the mitochondrial clearance or persistence in ECs or ISCs respectively. By mosaic genetic analysis, we then demonstrated that PINK1 and PARKIN function epistatically to mediate the specific timely removal of mitochondria, and are involved in global autophagy in ECs during Drosophila midgut metamorphosis, with kinase-dead PINK1 exerting dominant negative effects. Taken together, our studies concluded that the PINK1/PARKIN is crucial for timely cell-type specific mitophagy under physiological conditions and demonstrated again that Drosophila midgut metamorphosis might serve as an elegant in vivo model to study autophagy. [ABSTRACT FROM AUTHOR]