ALBERT

Description: This paper addresses the stabilization problem for a class of genetic regulatory networks (GRNs) with mixed delays which include both the finite distributed time delay and the discrete time delay. The adaptive feedback control scheme is adopted to achieve the global asymptotic stability for the GRNs. By resorting to the integral partitioning technique and the delay fractioning approach, a novel Lyapunov–Krasovskii functional is constructed, and some sufficient criteria are established to ensure the closed-loop GRNs to be globally asymptotically stable. The conditions obtained are in the form of matrix inequalities and easy to be solved by resorting to the standard softwares in the Matlab. Finally, a numerical example is given to demonstrate the applicability and efficiency of the proposed approach.

Description: Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant ( P 〈 5.0 x 10 –8 ) associations with blood pressure, which included variants at three new loci ( CACNA1D , CYP21A2 , and MED13L ) and a newly discovered variant near SLC4A7 . We also replicated 14 previously reported loci, 8 ( CASZ1 , MOV10 , FGF5 , CYP17A1 , SOX6 , ATP2B1 , ALDH2 , and JAG1 ) at genome-wide significance, and 6 ( FIGN , ULK4 , GUCY1A3 , HFE , TBX3-TBX5 , and TBX3 ) at a suggestive level of P = 1.81 x 10 –3 to 5.16 x 10 –8 . These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.

Description: This paper studies consensus problems of multi-agent systems over a directed network topology on time scales. Based on the theory of time scales, we discuss continuous-time and discrete-time consensus protocols under a unified framework by employing a Lyapunov-like technique. We find that consensus can be realized exponentially if the graininess function of the time scale is bounded and the coupling strength of the network is sufficiently small. Many existing results of both continuous-time and discrete-time consensus conditions are shown to be special cases of this paper. Moreover, our derived results contain both continuous-time and discrete-time cases simultaneously. Finally, several illustrative examples are presented to show the effectiveness of the theoretical results.

Description: 1, 3-Butadiene (BD) is a high-efficiency carcinogen in rodents and was classified as a human carcinogen in 2008 by the International Agency for Research on Cancer. However, its ability to induce genetic damage and the influence of metabolic polymorphisms to such damage in humans are both controversial claims. This study was conducted to investigate the relationships between exposure to BD, the polymorphisms of metabolic genes and the chromosomal damage in 45 pairs of occupationally exposed workers in a BD product workshop and matched control workers in an administrative office and circulatory water workshop in China. Exposure to BD was evaluated by personal sampling and stationary sampling. Different chromosomal damage endpoints in peripheral blood lymphocytes were determined using the cytokinesis-blocked micronucleus (CBMN) cytome assay; polymorphisms of metabolic genes [cytochrome P450 2E1 ( CYP2E1 ), glutathione S -transferases ( GST ) and microsomal epoxide hydrolase ( mEH )] in BD-exposed group were detected by polymerase chain reaction (PCR) or PCR–restriction fragment length polymorphism analysis. The results show that the average BD measurements of the exposed group were significantly higher than those for the control group (a personal sampling and stationary sampling, respectively). The BD-exposed workers exhibited increased frequencies of micronuclei (MNi) (8.00 ± 3.78 versus 5.62 ± 2.41) and nucleoplasmic bridges (NPBs) (2.58 ± 2.79 versus 1.13 ± 1.34) and a decreased nuclear division index (2.20 ± 0.14 versus 2.35 ± 0.27) when compared subjects in the control group. Meanwhile, BD-exposed workers carrying CYP2E1 c1c2/c2c2 or mEH intermediate (I)/high (H) group had a significantly higher NPB frequency than those carrying CYP2E1 c1c1 [frequency ratio (FR) = 2.60, 95% confidence interval (CI) 1.72–3.93; P 〈 0.0001) or the mEH low(S) group (FR = 2.06, 95% CI% 1.17–3.62; P 〈 0.05), respectively. Our study suggests that MNi and NPB frequency in CBMN cytome assay could be potential genotoxic biomarkers for BD exposure in humans. The polymorphism of CYP2E1 and mEH could also affect the chromosomal instability of BD workers.

Description: Motivation: The sequencing of over a thousand natural strains of the model plant Arabidopsis thaliana is producing unparalleled information at the genetic level for plant researchers. To enable the rapid exploitation of these data for functional proteomics studies, we have created a resource for the visualization of protein information and proteomic datasets for sequenced natural strains of A. thaliana . Results: The 1001 Proteomes portal can be used to visualize amino acid substitutions or non-synonymous single-nucleotide polymorphisms in individual proteins of A. thaliana based on the reference genome Col-0. We have used the available processed sequence information to analyze the conservation of known residues subject to protein phosphorylation among these natural strains. The substitution of amino acids in A. thaliana natural strains is heavily constrained and is likely a result of the conservation of functional attributes within proteins. At a practical level, we demonstrate that this information can be used to clarify ambiguously defined phosphorylation sites from phosphoproteomic studies. Protein sets of available natural variants are available for download to enable proteomic studies on these accessions. Together this information can be used to uncover the possible roles of specific amino acids in determining the structure and function of proteins in the model plant A. thaliana . An online portal to enable the community to exploit these data can be accessed at http://1001proteomes.masc-proteomics.org/ Contact: jlheazlewood@lbl.gov Supplementary information: Supplementary data are available at Bioinformatics online.

Description: 〈sec〉〈st〉Synopsis〈/st〉〈p〉〈textbox textbox-type="graphic"〉〈p〉〈inline-fig〉〈/inline-fig〉〈/p〉〈/textbox〉〈/p〉 〈p〉As abnormal TGF-β responses are linked to human diseases such as cancer, TGF-β signaling must be tightly regulated. This study uncovers a PTPN3 as regulator of Smurf2 binding to TβRI, a function that is abolished by hepatocarcinoma-associated mutations.〈/p〉 〈p〉 〈l type="unord"〉〈li〉〈p〉PTPN3 potentiates TGF-β signaling independent of its phosphatase activity.〈/p〉〈/li〉 〈li〉〈p〉PTPN3 stabilizes TGF-β type I receptor by inhibiting its interaction with Smurf2.〈/p〉〈/li〉 〈li〉〈p〉L232R mutation associated with intrahepatic cholangiocarcinoma interferes with the TGF-β activatory and tumor suppressive functions of PTPN3.〈/p〉〈/li〉〈/l〉 〈/p〉〈/sec〉

Description: Oil and gas reservoirs can cause anomalies in the energy and frequency of seismic signals. We can take advantage of these anomalies for hydrocarbon detection. Based on the Teager–Kaiser (TK) energy characteristics, a method that uses this energy in association with the Empirical Mode Decomposition (EMD) method is proposed for hydrocarbon detection in carbonate reservoirs. The EMD method, which can decompose the original seismic signals into a finite number of monocomponent intrinsic mode functions (IMFs) in the temporal domain, is used for multiband filtering. A TK energy separation algorithm is used to estimate the instantaneous frequency and amplitude of the selected IMFs from the EMD method. The proposed method can generate a joint time–frequency representation that can reflect the energy tracking of the seismic signals. The instantaneous spectrums produced by the EMD/TK method have the capability to detect hydrocarbon. The model results to the gas field, which located in the eastern Ordos Basin, China, show that the EMD/TK method can be adopted and they detect the gas-bearing reservoir efficiently. Application of the EMD/TK method in hydrocarbon detection in a gas field located in the Eastern Ordos Basin shows its effectiveness. The EMD/TK method can be used as a new analysis tool to determine the instantaneous spectral properties of a reservoir to detect hydrocarbon.

Description: Author(s): W. Fan, J. Cao, J. Seidel, Y. Gu, J. W. Yim, C. Barrett, K. M. Yu, J. Ji, R. Ramesh, L. Q. Chen, and J. Wu Superheating and supercooling effects are characteristic kinetic processes in first-order phase transitions, and asymmetry between them is widely observed. In materials where electronic and structural degrees of freedom are coupled, a wide, asymmetric hysteresis may occur in the transition between e... [Phys. Rev. B 83, 235102] Published Thu Jun 02, 2011

Description: The proposal that enzymatic catalysis is due to conformational fluctuations has been previously promoted by means of indirect considerations. However, recent works have focused on cases where the relevant motions have components toward distinct conformational regions, whose population could be manipulated by mutations. In particular, a recent work has claimed to provide direct experimental evidence for a dynamical contribution to catalysis in dihydrofolate reductase, where blocking a relevant conformational coordinate was related to the suppression of the motion toward the occluded conformation. The present work utilizes computer simulations to elucidate the true molecular basis for the experimentally observed effect. We start by reproducing the trend in the measured change in catalysis upon mutations (which was assumed to arise as a result of a “dynamical knockout” caused by the mutations). This analysis is performed by calculating the change in the corresponding activation barriers without the need to invoke dynamical effects. We then generate the catalytic landscape of the enzyme and demonstrate that motions in the conformational space do not help drive catalysis. We also discuss the role of flexibility and conformational dynamics in catalysis, once again demonstrating that their role is negligible and that the largest contribution to catalysis arises from electrostatic preorganization. Finally, we point out that the changes in the reaction potential surface modify the reorganization free energy (which includes entropic effects), and such changes in the surface also alter the corresponding motion. However, this motion is never the reason for catalysis, but rather simply a reflection of the shape of the reaction potential surface.

Description: Substantial evidence has confirmed that Polo-like kinases (Plks) play a crucial role in a variety of cellular processes via phosphorylation-mediated signaling transduction. Identification of Plk phospho-binding proteins and phosphorylation substrates is fundamental for elucidating the molecular mechanisms of Plks. Here, we present an integrative approach for the analysis of Plk-specific phospho-binding and phosphorylation sites (p-sites) in proteins. From the currently available phosphoproteomic data, we predicted tens of thousands of potential Plk phospho-binding and phosphorylation sites in eukaryotes, respectively. Furthermore, statistical analysis suggested that Plk phospho-binding proteins are more closely implicated in mitosis than their phosphorylation substrates. Additional computational analysis together with in vitro and in vivo experimental assays demonstrated that human Mis18B is a novel interacting partner of Plk1, while p T14 and p S48 of Mis18B were identified as phospho-binding sites. Taken together, this systematic analysis provides a global landscape of the complexity and diversity of potential Plk-mediated phosphoregulation, and the prediction results can be helpful for further experimental investigation.