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Acute myocardial infarction (AMI) is the leading cause of death worldwide. Ischemia-reperfusion (I/R) injury is considered the most common contributor to AMI. Hirsutine has been shown to protect cardiomyocytes against hypoxic injury. The present study investigated whether hirsutine improved AMI induced by I/R injury and the underlying mechanisms. In our study, we used a rat model of myocardial I/R injury. The rats were given hirsutine daily (5, 10, 20 mg/kg) by gavage for 15 days before the myocardial I/R injury. Detectable changes were observed in myocardial infarct size, mitochondrial function, histological damage, and cardiac cell apoptosis. According to our findings, hirsutine pretreatment reduced the myocardial infarct size, enhanced cardiac function, inhibited cell apoptosis, reduced the tissue lactate dehydrogenase (LDH) and reactive oxygen species (ROS) content, as well as enhanced myocardial ATP content and mitochondrial complex activity. In addition, hirsutine balanced mitochondrial dynamics by increasing Mitofusin2 (Mfn2) expression while decreasing dynamin-related protein 1 phosphorylation (p-Drp1), which was partially regulated by ROS and calmodulin-dependent protein kinase II phosphorylation (p-CaMKII). Mechanistically, hirsutine inhibited mitochondrial-mediated apoptosis during I/R injury by blocking the AKT/ASK-1/p38 MAPK pathway. This present study provides a promising therapeutic intervention for myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Ultra-deep carbonate gas reservoirs are buried at great depths and have high temperatures, and the impact of high temperature on the seepage capacity of multi-type reservoirs is still unclear. The study selected cores from the fourth member of Dengying Formation in the Gaoshiti-Moxi area to measure the gas single-phase permeability of rock samples during the heating and cooling process, as well as the gas-water interfacial tension and gas-water two-phase relative permeability at different temperatures. This allowed researchers to obtain the effect of temperature on the seepage capacity of multi-type ultra-deep carbonate gas reservoir. The research results show that within the range of 20-120 °C, with the change of temperature, the gas single-phase seepage capacity of different types of reservoir rock samples changes as a power function. The decrease in gas-phase permeability during the heating process is jointly affected by the increase in gas viscosity, the expansion of dolomite crystals, and the migration of rock particles after embrittlement. After one heating and cooling process, fractured-cavity type rock samples had the highest irreversible degree of permeability at 82.52%, due to the development of micro-fractures, followed by 27.63% for pore type due to the development of small pores and throats, and the lowest was 9.46% for pore-cavity type. Fractured-cavity rock samples are temperature-sensitive, while pore-type and pore-cavity-type rock samples are temperature-resistant. The upper-temperature limit of the target multi-type gas reservoir is concentrated around 46-50 °C. The temperature increase mainly improves the gas-displacing water efficiency and gas-water two-phase seepage capacity by reducing the water-gas viscosity ratio, which is about 1/3 of the normal temperature at the formation temperature. The gas-water phase permeability curves of multi-type reservoirs under high-temperature conditions can better represent the two-phase seepage characteristics of actual formations. The effect of temperature on the seepage capacity of multi-type ultra-deep carbonate gas reservoirs can provide a theoretical basis for the efficient development of such gas reservoirs. [ABSTRACT FROM AUTHOR]

The article presents a study that explores serpentinite-derived slab fluids control the oxidation state of the subarc mantle. It mentions that primitive arc magmas associated with flat, warm subduction as less oxidized overall than those generated in steep, cold subduction zones. It discusses the establishment a link between deep subduction-related fluids derived from dehydration of serpentinite altered oceanic crust (AOC) using B isotopes and B/Nb as fluid proxies.

With the continuous development of society and economy, people’s demand for electric energy is increasing. The low-carbon and energy-saving technologies of renewable energy especially wave energy have become the focus of current researches. Considering the increasingly serious energy problems, a wave energy converter (WEC) is proposed based on Halbach permanent magnetic array, which increases the output performance. The equivalent magnetic circuit model of the WEC is established. The static magnetic field modeling and structural parameters optimal permanent of the WEC are performed on this theoretical. Theoretical studies have found that the optimal permanent magnet thickness ratios for Halbach permanent magnet array structures is 0.6, and the ratio of permanent magnet to coil radial ratio is 0.7. The coil winding form and rectifying circuit of the WEC were designed. The WEC equivalent magnetic circuit model was verified by COMSOL Multiphysics finite element software, and the open circuit voltages of WEC was obtained. If the WEC moves at a speed of 0.1 m/s, the coil voltage can reach about 113 V after simulation. According to the testing requirements of the WEC, a test platform was built. The Halbach permanent magnet array structures greatly enhances the wave energy collection of WEC. [ABSTRACT FROM AUTHOR]

Mild replication stress enhances appearance of dozens of robust recurrent genomic break clusters, termed RDCs, in cultured primary mouse neural stem and progenitor cells (NSPCs). Robust RDCs occur within genes (“RDC-genes”) that are long and have roles in neural cell communications and/or have been implicated in neuropsychiatric diseases or cancer. We sought to develop an in vitro approach to determine whether specific RDC formation is associated with neural development. For this purpose, we adapted a system to induce neural progenitor cell (NPC) development from mouse embryonic stem cell (ESC) lines deficient for XRCC4 plus p53, a genotype that enhances DNA double-strand break (DSB) persistence to enhance detection. We tested for RDCs by our genome-wide DSB identification approach that captures DSBs via their ability to join to specific genomic Cas9/single-guide RNA–generated bait DSBs. In XRCC4/p53-deficient ESCs, we detected seven RDCs, all of which were in genes and two of which were robust. In contrast, in NPCs derived from these ESC lines we detected 29 RDCs, a large fraction of which were robust and associated with long, transcribed neural genes that were also robust RDC-genes in primary NSPCs. These studies suggest that many RDCs present in NSPCs are developmentally influenced to occur in this cell type and indicate that induced development of NPCs from ESCs provides an approach to rapidly elucidate mechanistic aspects of NPC RDC formation. [ABSTRACT FROM AUTHOR]

Background: The development of chromosomal conformation capture techniques, particularly, the Hi-C technique, has made the analysis and study of the spatial conformation of a genome an important topic in bioinformatics and computational biology. Aided by high-throughput next generation sequencing techniques, the Hi-C technique can generate genome-wide, large-scale intra- and inter-chromosomal interaction data capable of describing in details the spatial interactions within a genome. These data can be used to reconstruct 3D structures of chromosomes that can be used to study DNA replication, gene regulation, genome interaction, genome folding, and genome function. Results: Here, we introduce a maximum likelihood algorithm called 3DMax to construct the 3D structure of a chromosome from Hi-C data. 3DMax employs a maximum likelihood approach to infer the 3D structures of a chromosome, while automatically re-estimating the conversion factor (α) for converting Interaction Frequency (IF) to distance. Our results show that the models generated by 3DMax from a simulated Hi-C dataset match the true models better than most of the existing methods. 3DMax is more robust to structural variability and noise. Compared on a real Hi-C dataset, 3DMax constructs chromosomal models that fit the data better than most methods, and it is faster than all other methods. The models reconstructed by 3DMax were consistent with fluorescent in situ hybridization (FISH) experiments and existing knowledge about the organization of human chromosomes, such as chromosome compartmentalization. Conclusions: 3DMax is an effective approach to reconstructing 3D chromosomal models. The results, and the models generated for the simulated and real Hi-C datasets are available here: http://sysbio.rnet.missouri.edu/bdm_download/3DMax/. The source code is available here: https://github.com/BDM-Lab/3DMax. A short video demonstrating how to use 3DMax can be found here: https://youtu.be/ehQUFWoHwfo. [ABSTRACT FROM AUTHOR]

The field of civil engineering is in need of new methods of non-destructive testing, especially in order to prevent and monitor the serious deterioration of concrete structures. In this work, experimental results are reported on fault detection and characterization in a meter-scale concrete structure using an ultrasonic nonlinear coda wave interferometry (NCWI) method. This method entails the nonlinear mixing of strong pump waves with multiple scattered probe (coda) waves, along with analysis of the net effect using coda wave interferometry. A controlled damage protocol is implemented on a post-tensioned, meter-scale concrete structure in order to generate cracking within a specific area being monitored by NCWI. The nonlinear acoustic response due to the high amplitude of acoustic modulation yields information on the elastic nonlinearities of concrete, as evaluated by two specific nonlinear observables. The increase in nonlinearity level corresponds to the creation of a crack with a network of microcracks localized at its base. In addition, once the crack closes as a result of post-tensioning, the residual nonlinearities confirm the presence of the closed crack. Last, the benefits and applicability of this NCWI method to the characterization and monitoring of large structures are discussed. [ABSTRACT FROM AUTHOR]

Target detection from hyperspectral images is an important problem but encounters a critical challenge of simultaneously reducing spectral redundancy and preserving the discriminative information. Recently, the joint sparse representation and multi-task learning (JSR-MTL) approach was proposed to address the challenge. However, it does not fully explore the prior class label information of the training samples and the difference between the target dictionary and background dictionary when constructing the model. Besides, there may exist estimation bias for the unknown coefficient matrix with the use of l1/l2 minimization which is usually inconsistent in variable selection. To address these problems, this paper proposes an adaptive joint sparse representation and multi-task learning detector with locality information (JSRMTL-ALI). The proposed method has the following capabilities: (1) it takes full advantage of the prior class label information to construct an adaptive joint sparse representation and multi-task learning model; (2) it explores the great difference between the target dictionary and background dictionary with different regularization strategies in order to better encode the task relatedness; (3) it applies locality information by imposing an iterative weight on the coefficient matrix in order to reduce the estimation bias. Extensive experiments were carried out on three hyperspectral images, and it was found that JSRMTL-ALI generally shows a better detection performance than the other target detection methods. [ABSTRACT FROM AUTHOR]

Hepatocyte nuclear factor 6 (HNF6) is required for liver development, but its role in adult liver metabolism is not known. Here we show that deletion of HNF6 in livers of adult C57Bl/6 mice leads to hepatic steatosis in mice fed normal laboratory chow. Although HNF6 is known mainly as a transcriptional activator, hepatic loss of HNF6 up-regulated many lipogenic genes bound directly by HNF6. Many of these genes are targets of the circadian nuclear receptor Rev-erbα, and binding of Rev-erbα at these sites was lost when HNF6 was ablated in the liver. While HNF6 and Rev-erbα coordinately regulate hepatic lipid metabolism, each factor also affects additional gene sets independently. These findings highlight a novel mechanism of transcriptional repression by HNF6 and demonstrate how overlapping and distinct mechanisms of transcription factor function contribute to the integrated physiology of the liver. [ABSTRACT FROM AUTHOR]

This paper describes the use of an ultrasonic imaging technique (Locadiff) for the Non-Destructive Testing & Evaluation of a concrete structure. By combining coda wave interferometry and a sensitivity kernel for diffuse waves, Locadiff can monitor the elastic and structural properties of a heterogeneous material with a high sensitivity, and can map changes of these properties over time when a perturbation occurs in the bulk of the material. The applicability of the technique to life-size concrete structures is demonstrated through the monitoring of a 15-ton reinforced concrete beam subject to a four-point bending test causing cracking. The experimental results show that Locadiff achieved to (1) detect and locate the cracking zones in the core of the concrete beam at an early stage by mapping the changes in the concrete's micro-structure; (2) monitor the internal stress level in both temporal and spatial domains by mapping the variation in velocity caused by the acoustoelastic effect. The mechanical behavior of the concrete structure is also studied using conventional techniques such as acoustic emission, vibrating wire extensometers, and digital image correlation. The performances of the Locadiff technique in the detection of early stage cracking are assessed and discussed. [ABSTRACT FROM AUTHOR]

As a typical kinds of toxic gases, CO plays an important role in environmental monitoring, control of chemical processes, space missions, agricultural and medical applications. Graphene is considered a potential candidate of gases sensor, so the adsorption of CO molecules on various graphene, including pristine graphene, Nitrogen-doped graphene (N-doped graphene) and Aluminum-doped graphene (Al-doped graphene), are studied by using first-principles calculations. The optimal configurations, adsorption energies, charge transfer, and electronic properties including band structures, density of states and differential charge density are obtained. The adsorption energies of CO molecules on pristine graphene and N-doped graphene are -0.01 eV, and -0.03 eV, respectively. In comparison, the adsorption energy of CO on Al-doped graphene is much larger, -2.69 eV. Our results also show that there occurs a large amount of charge transfer between CO molecules and graphene sheet after the adsorption, which suggests Al-doped graphene is more sensitive to the adsorption of CO than pristine graphene and N-doped graphene. Therefore, the sensitivity of gases on graphene can be drastically improved by introducing the suitable dopants. [ABSTRACT FROM AUTHOR]

Many biological populations fluctuate in synchrony over large geographic regions. This behavior may increase the chance of extinction. The combination of time-scale separation between interacting species and weak spatial linear diffusive coupling is one mechanism that can generate synchrony; however, accounting for travel time between habitat patches may destabilize this synchrony. Here, we show that ubiquitous behavioral aspects of dispersal (e.g., predator avoidance), implemented as nonlinear diffusive coupling, may also destabilize synchrony. In addition, these aspects interact with travel-time delays and amplify mechanisms that destroy synchrony. Our work suggests that dispersal-induced synchrony is more rare than typically assumed. [ABSTRACT FROM AUTHOR]

The article discusses research on the genomic mechanisms used by the transcript factor (TF) and nuclear receptor Rev-erba to modulate the body's clock and metabolism. Topics include Rev-erba's clock control through binding directly to genomes to compete with activating ROR TFs, Rev-erba's recruitment of the HDAC3 co-repressor to sites to which its tethered by cell-type transcription factors to regulate metabolism, and the use of lineage-determining factors to convey epigenomic rhythm to tissues.

In this paper, a new sparse representation-based binary hypothesis (SRBBH) model for hyperspectral target detection is proposed. The proposed approach relies on the binary hypothesis model of an unknown sample induced by sparse representation. The sample can be sparsely represented by the training samples from the background-only dictionary under the null hypothesis and the training samples from the target and background dictionary under the alternative hypothesis. The sparse vectors in the model can be recovered by a greedy algorithm, and the same sparsity levels are employed for both hypotheses. Thus, the recovery process leads to a competition between the background-only subspace and the target and background subspace, which are directly represented by the different hypotheses. The detection decision can be made by comparing the reconstruction residuals under the different hypotheses. Extensive experiments were carried out on hyperspectral images, which reveal that the SRBBH model shows an outstanding detection performance. [ABSTRACT FROM PUBLISHER]

The outer strap as a typical structure of a spacer grid enhances the mechanical strength, decreases hang-up susceptibility, and also influences thermal hydraulic performance, for example, pressure loss, mixing performance, and flow distribution. In the present study, a typical grid spacer with different outer strap designs is adopted to investigate the influence of outer strap design on fuel assembly thermal hydraulic performance by using a commercial computational fluid dynamics (CFD) code, ANSYS CFX, and a subchannel analysis code, FLICA. To simulate the outer straps' influence between fuel assemblies downstream, four quarter-bundles from neighboring fuel assemblies are constructed to form the computational domain. The results show that the outer strap design has a major impact on cross-flow between fuel assemblies and temperature distribution within the fuel assembly. [ABSTRACT FROM AUTHOR]

This paper is devoted to the study of a reaction-diffusion Lyme disease model with seasonality. In the case of a bounded habitat, we obtain a threshold result on the global stability of either disease-free or endemic periodic solution. In the case of an unbounded habitat, we establish the existence of the disease spreading speed and its coincidence with the minimal wave speed for time-periodic traveling wave solutions. We also estimate parameter values based on some published data and use them to study the Lyme disease transmission in Port Dove, Ontario. Our numerical simulations are consistent with the obtained analytic results. [ABSTRACT FROM AUTHOR]

This paper is devoted to the study of a periodic reaction—diffusion competition model, which describes the propagation of two competitive species in bad and good seasons. The existence and global stability of time-periodic bistable travelling waves are established for such a system under appropriate conditions. The methods involve the upper and lower solutions, spreading speeds of monostable systems, and the monotone semiflows approach. [ABSTRACT FROM AUTHOR]

Typically, the Electromechanical Impedance (EMI) technique does not use an analytical model for basic damage identification. However, an accurate model is necessary for getting more information about any damage. In this paper, an EMI model is presented for predicting the electromechanical impedance of a cracked beam structure quantitatively. A coupled system of a cracked Timoshenko beam with a pair of PZT patches bonded on the top and bottom surfaces has been considered, where the bonding layers are assumed as a Kelvin-Voigt material. The shear lag model is introduced to describe the load transfer between the PZT patches and the beam structure. The beam crack is simulated as a massless torsional spring; the dynamic equations of the coupled system are derived, which include the crack information and the inertial forces of both PZT patches and adhesive layers. According to the boundary conditions and continuity conditions, the analytical expression of the admittance of PZT patch is obtained. In the case study, the influences of crack and the inertial forces of PZT patches are analyzed. The results show that: (1) the inertial forces affects significantly in high frequency band; and (2) the use of appropriate frequency range can improve the accuracy of damage identification. [ABSTRACT FROM AUTHOR]

We have successfully fabricated a glass microfluidic device with a confined T-shaped junction in an ordinary laboratory without a clean room. In the microfluidic T-shaped junction, the bubble formation regime and the bubble volume generated were studied under different combinations of gas inlet pressure, liquid flow rate, liquid viscosity, and surface tension. It was found that both the minimum and the maximum gas inlet pressures for generating bubbles were larger than and proportional to the liquid pressure drop from the T-shaped junction to the channel outlet. The capillary number was found to have a significant influence on the bubble volume. An empirical relation is proposed to predict the bubble volume based on the capillary number and the liquid pressure drop from the T-shaped junction to the channel outlet. [ABSTRACT FROM AUTHOR]

The multiple intersecting stiffeners on the chemical milling stiffened panel (CMSP) limit the application of active health monitoring methods on it. An imaging algorithm based on electromechanical impedance (EMI) and probability-weighting is proposed to achieve quantitative evaluation and localization of the damage on CMSP. The proposed algorithm compensates for the difference in sensor performance with coefficients and there is no need to determine the key parameters of the algorithm through prior experiments. In the paper, the applicability of ultrasonic guided wave (GW) and EMI on CMSP was first studied through the finite element method. Based on EMI and the mean absolute percentage deviation (MAPD), the selected damage indicator (DI), a probability-weighted damage imaging algorithm are proposed and experimentally verified. The results indicate that due to the reflection and attenuation effects of stiffeners on GW, the signal characteristics of damage scattering waves are contaminated, making it difficult to quantitatively characterize the damage from GW signals through DIs. MAPD is positively correlated with the damage degree and has consistency in characterizing the signal of different PZTs under the same working condition. The feasibility and accuracy of the proposed algorithm are verified through experiments which show a strong engineering application capability. [ABSTRACT FROM AUTHOR]

The induction of seed dormancy and its release involve a finely regulated genetic program controlled by various environmental and developmental cues that are critical for plant survival and population expansion. Light plays a key role in seed dormancy and germination, but the molecular mechanisms underlying the control of dormancy are unclear. In the present study, high-resolution temporal RNA-seq in Arabidopsis identified WOX11 as encoding a hub transcription factor during the seed dormancy induction and release stages. This gene might have evolved from gymnosperms and expanded in angiosperms with highly conserved expression patterns in seeds. WOX11 and its homolog WOX12 were highly expressed from 2 d after pollination, and mRNA abundance was greatly increased during the seed dormancy induction and release stages. Further, we found that WOX11 plays a role in the regulation of seed dormancy downstream of phytochrome B (PHYB)-mediated red-light signaling during the induction stage, indicating that WOX11/12 are newly identified components of red-light signaling transduction. Taken together, our results suggest that WOX11/12-mediated PHYB signaling regulates seed dormancy in Arabidopsis, and provide insights into the developmental regulation and evolutionary adaptation of plants to changes in the light environment. [ABSTRACT FROM AUTHOR]

Antibody heavy chain (HC) and light chain (LC) variable region exons are assembled by V(D)J recombination. V(D)J junctional regions encode complementarity-determining-region 3 (CDR3), an antigen-contact region immensely diversified through nontemplated nucleotide additions ("N-regions") by terminal deoxynucleotidyl transferase (TdT). HIV-1 vaccine strategies seek to elicit human HIV-1 broadly neutralizing antibodies (bnAbs), such as the potent CD4-binding site VRC01-class bnAbs. Mice with primary B cells that express receptors (BCRs) representing bnAb precursors are used as vaccination models. VRC01-class bnAbs uniformly use human HC VH1-2 and commonly use human LCs Vκ3-20 or Vκ1-33 associated with an exceptionally short 5-amino-acid (5-aa) CDR3. Prior VRC01-class models had nonphysiological precursor levels and/or limited precursor diversity. Here, we describe VRC01-class rearranging mice that generate more physiological primary VRC01-class BCR repertoires via rearrangement of VH1-2, as well as Vκ1-33 and/or Vκ3-20 in association with diverse CDR3s. Human-like TdT expression in mouse precursor B cells increased LC CDR3 length and diversity and also promoted the generation of shorter LC CDR3s via N-region suppression of dominant microhomology-mediated Vκ-to-Jκ joins. Priming immunization with eOD-GT8 60mer, which strongly engages VRC01 precursors, induced robust VRC01-class germinal center B cell responses. Vκ3-20-based responses were enhanced by N-region addition, which generates Vκ3-20-to-Jκ junctional sequence combinations that encode VRC01- class 5-aa CDR3s with a critical E residue. VRC01-class-rearranging models should facilitate further evaluation of VRC01-class prime and boost immunogens. These new VRC01-class mouse models establish a prototype for the generation of vaccine-testing mouse models for other HIV-1 bnAb lineages that employ different HC or LC Vs. [ABSTRACT FROM AUTHOR]

In previous work, we have developed a simple strategy for a label-free and separation-free bioassay for target DNA and protein, with the limit of detection at the nM level only. Herein, taking advantage of atomic fluorescence spectrometric detection of metal ions and amplification of DNA, a label-free and separation-free ultrasensitive homogeneous DNA analytical platform for target DNA and protein detection was developed on the basis of an enzyme-free strand displacement signal amplification strategy for dramatically improved detectability. Using the T- Hg2+-T hairpin structure as the probe, the target DNA binds with HP (T-Hg2+-T hairpin structure) and released the Hg2+ first; then, the P4 (help DNA) hybridizes with target-P3 complex and free the target DNA, which is used to trigger another reaction cycle. The cycling use of the target amplifies the mercury atomic fluorescence intensity for ultrasensitive DNA detection. Moreover, the enzyme-free strand displacement signal amplification analytical system was further extended for protein detection by introducing an aptamer-P2 arched structure with thrombin as a model analyte. The current homogeneous strategy provides an ultrasensitive AFS detection of DNA and thrombin down to the 0.3 aM and 0.1 aM level, respectively, with a high selectivity. This strategy could be a promising unique alternative for nucleic acid and protein assay. [ABSTRACT FROM AUTHOR]

Intrinsic microcrystalline silicon thin film were prepared by VHF-PECVD, the activation energy of thin film were measured by activation energy testing equipment. The activation energy of samples with different crystalline volume fraction and prepared at different power and different pressure were studied. The results showed that: the activation energy of samples deposited at amorphous/microcrystalline transition zone decrease as crystalline volume fraction increasing. With increasing of depositing power and pressure, the depositing rate were increased, the activation energy were also increased, the oxygen contaminate could be suppressed by increasing depositing rate by increasing depositing power and pressure. [ABSTRACT FROM AUTHOR]

The genetic causes of idiopathic premature ovarian insufficiency (POI) and nonobstructive azoospermia (NOA) remain unclear. We performed whole-exome sequencing (WES) in members of a consanguineous family with two POI and two NOA patients to screen for potential pathogenic variants for familial POI and NOA. And a homozygous variant in SPATA22 (c.400C>T:p.R134X) was identified. Histological analysis and spermatocyte spreading assay demonstrated that the spermatogenesis was arrested at a zygotene-like stage in the proband with NOA. The candidate gene was further screened in the in-house WES database of idiopathic POI-affected patients. One additional compound heterozygous variant in SPATA22 (c.900+1G>A and c.31C>T:p.R11X) was found in one patient with sporadic POI and validated by minigene assay. Thus, this is the first report identifying SPATA22 as the causative gene for human POI. Combined with the observations in the familial patient with NOA, our findings highlighted the essential role of meiotic HR genes in gametogenesis and gonadal function maintenance. [ABSTRACT FROM AUTHOR]

The article focuses on the role of the lipid globotriaosylceramide (Gb3) in promoting germinal center B cell responses and antiviral immunity. Topics include Gb3's specific binding to CD19, facilitating BCR signaling and affinity maturation, as well as its regulation of MHC-II levels to enhance antibody diversity, ultimately proposing Gb3 as a potential adjuvant for viral infection vaccination.

The threonine and serine protein kinase AKT plays a major role in inhibiting apoptosis in a number of malignant cell types including prostate and breast carcinoma. Activation of AKT is a complex process involving translocation to the plasma membrane and phosphorylation of serine and threonine amino-acid residues. We now report that the novel compound 4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC), induces apoptosis in breast and prostate carcinoma cells and inhibits AKT activity in these cells. Overexpression of a constitutively activated AKT inhibits 3-Cl-AHPC-mediated apoptosis. Decrease in AKT activity occurs through 3-Cl-AHPC inhibition of phosphatidylinositol 3 kinase (PI3-K) activity. 3-Cl-AHPC inhibits PI3-K activity by enhancing epidermal growth factor receptor (EGFR) proteolysis and thus inhibiting EGFR association with the p85 subunit of PI3-K. 3-Cl-AHPC-mediated decrease in PI3-K activity results in the reduced synthesis of phosphatidylinositol 3,4 bisphosphate and phosphatidylinositol 3,4,5 triphosphate with the subsequent inhibition of integrin-linked kinase activity and serine-473 phosphorylation of AKT. Overexpression of EGFR results in increased AKT activity and inhibition of 3-Cl-AHPC-mediated decrease in AKT activation, AKT activity and 3-Cl-AHPC-mediated apoptosis. Inhibition of AKT activity by this compound results in the inability of AKT to phosphorylate and inactivate the proapoptotic forkhead transcription factor.Oncogene (2004) 23, 1874-1884. doi:10.1038/sj.onc.1207311 Published online 23 February 2004 [ABSTRACT FROM AUTHOR]

Background: After the one-child policy has been effective for over 30 years, China implemented the universal two-child policy in 2015. The number of high-risk pregnant women had increased dramatically ever since, increasing negative health outcomes for both mothers and children. Our study aims to investigate the status of anxiety, psychological stress sources, and psychological capital among women pregnant with a second child, and to assess influencing factors and correlations, providing scientific basis for promoting women's health during pregnancy.Methods: We recruited 513 participants from maternity hospitals in Guangdong and Shandong Province. All participants completed the Zung Self-Rating Anxiety Scale (SAS), Pregnant women psychological stress sources questionnaire and the psychological capital questionnaire (PCQ-24).Results: The prevalence of anxiety of women pregnant with a second child was 27.5%. The score of psychological stress sources was 74.93 ± 16.07. The risk factors for the anxiety of the women pregnant with a second child included low education level of the husband, gender expectation and the sources of psychological stress of the pregnant woman. The risk factors for psychological stress were dissatisfaction of residence and unplanned pregnancy. The main factors influencing psychological capital were the participants' education level, whether they have learned antenatal care knowledge and satisfaction with the residence.Limitations: All participants were recruited only from tertiary hospitals in Guangdong and Shandong province.Conclusions: Anxiety and psychological stress is prevalent during pregnancy among women pregnant with a second child in Guangdong and Shandong. Psychological capital was a protective factor for anxiety. [ABSTRACT FROM AUTHOR]

We recently discovered 27 recurrent DNA double-strand break (DSB) clusters (RDCs) in mouse neural stem/progenitor cells (NSPCs). Most RDCs occurred across long, late-replicating RDC genes and were found only after mild inhibition of DNA replication. RDC genes share intriguing characteristics, including encoding surface proteins that organize brain architecture and neuronal junctions, and are genetically implicated in neuropsychiatric disorders and/or cancers. RDC identification relies on high-throughput genome-wide translocation sequencing (HTGTS), which maps recurrent DSBs based on their translocation to "bait" DSBs in specific chromosomal locations. Cellular heterogeneity in 3D genome organization allowed unequivocal identification of RDCs on 14 different chromosomes using HTGTS baits on three mouse chromosomes. Additional candidate RDCs were also implicated, however, suggesting that some RDCs were missed. To more completely identify RDCs, we exploited our finding that joining of two DSBs occurs more frequently if they lie on the same cis chromosome. Thus, we used CRISPR/Cas9 to introduce specific DSBs into each mouse chromosome in NSPCs that were used as bait for HTGTS libraries. This analysis confirmed all 27 previously identified RDCs and identified many new ones. NSPC RDCs fall into three groups based on length, organization, transcription level, and replication timing of genes within them. While mostly less robust, the largest group of newly defined RDCs share many intriguing characteristics with the original 27. Our findings also revealed RDCs in NSPCs in the absence of induced replication stress, and support the idea that the latter treatment augments an already active endogenous process. [ABSTRACT FROM AUTHOR]

Background: Canine parvovirus (CPV) type 2 emerged in 1978 in the USA and quickly spread among dog populations all over the world with high morbidity. Although CPV is a DNA virus, its genomic substitution rate is similar to some RNA viruses. Therefore, it is important to trace the evolution of CPV to monitor the appearance of mutations that might affect vaccine effectiveness. Results: Our analysis shows that the VP2 genes of CPV isolated from 1979 to 2016 are divided into six groups: GI, GII, GIII, GIV, GV, and GVI. Amino acid mutation analysis revealed several undiscovered important mutation sites: F267Y, Y324I, and T440A. Of note, the evolutionary rate of the CPV VP2 gene from Asia and Europe decreased. Codon usage analysis showed that the VP2 gene of CPV exhibits high bias with an ENC ranging from 34.93 to 36.7. Furthermore, we demonstrate that natural selection plays a major role compared to mutation pressure driving CPV evolution. Conclusions: There are few studies on the codon usage of CPV. Here, we comprehensively studied the genetic evolution, codon usage pattern, and evolutionary characterization of the VP2 gene of CPV. The novel findings revealing the evolutionary process of CPV will greatly serve future CPV research. [ABSTRACT FROM AUTHOR]

Understanding how the brain captures transient experience and converts it into long lasting changes in neural circuits requires the identification and investigation of the specific ensembles of neurons that are responsible for the encoding of each experience. We have developed a Robust Activity Marking (RAM) system that allows for the identification and interrogation of ensembles of neurons. The RAM system provides unprecedented high sensitivity and selectivity through the use of an optimized synthetic activity-regulated promoter that is strongly induced by neuronal activity and a modified Tet-Off system that achieves improved temporal control. Due to its compact design, RAM can be packaged into a single adeno-associated virus (AAV), providing great versatility and ease of use, including application to mice, rats, flies, and potentially many other species. Cre-dependent RAM, CRAM, allows for the study of active ensembles of a specific cell type and anatomical connectivity, further expanding the RAM system's versatility. [ABSTRACT FROM AUTHOR]

Background: In our previous study, we had assessed in the Chinese Han population the association of KCNB1 rs1051295 with metabolic traits indicating metabolic syndrome, and showed that KCNB1 rs1051295 genotype TT was associated with increase of waist to hip ratio (WHR), fasting insulin (FINS), triglycerides (TG) and decreased insulin sensitivity at basal condition. Here, we aimed at detecting whether there were associations between other tag SNPs of KCNB1 and favorable or unfavorable metabolic traits. Methods: We conducted a case-control design of population-based cross-sectional study to investigate the association between each of the 22 candidates tag SNPs of KCNB1 and metabolic traits in a population of 733 Chinese Han individuals. The association was assessed by multiple linear regression analysis or unconditional logistic regression analysis. Results: We found that among the 22 selected tag SNPs, four were associated with an increase (rs3331, rs16994565) or decrease (rs237460, rs802950) in serum cholesterol levels; two of these (rs237460, rs802590) further associated or were associated with reduced serum LDL-cholesterol. Two novel tag SNPs (rs926672, rs1051295) were associated with increased serum TG levels. We also showed that KCNB1 rs926672 associated with insulin resistance by a case-control study, and two tag SNPs (rs2057077and rs4810952) of KCNB1 were associated with the measure of insulin resistance (HOMA-IR) in a cross-section study. Conclusion: These results indicate that KCNB1 is likely associated with metabolic traits that may either predispose or protect from progression to metabolic syndrome. This study provides initial evidence that the gene variants of KCNB1, encoding Kv2.1 channel, is associated with perturbation of lipid metabolism and insulin resistance in Chinese Han population. [ABSTRACT FROM AUTHOR]

Recovery of butyl acetate (BA) in the wastewater from solvent extraction of penicillin by solvent sublation into n-nonane is studied. Emulsification at water-solvent interface in the sublation was discussed, and nonpolar n-nonane was representatively used as the immiscible organic solvent to minimize the emulsification. Effects of operation variables, such as gas flow rate, Qa, and initial solvent volume, voi, were explored. Gas flow rate, Qa, was an important operation parameter and initial volume of solvent, voi, had a little effect on the sublation efficiency, Ess which could be more than 65% under optimal operation conditions with semibatch sublation after about 180 min operation. Experimental results also showed the axial concentration of BA along the column height first increased and then decreased from bottom to top because of the mutual effect of diverse mass transports. With initial concentration of BA in the wastewater of about 1%, the volume of solvent, vo, could be increased by more than 30% at the end of the sublation. Qualified butyl acetate could be obtained through distillation and n-nonane obtained could be recycled in the solvent sublation. Air stripping was not so effective as sublation in the recovery of BA. The sublation was carried out in a sieve plate column. Experimental results showed the sieve plate could increase the axial Peclet number of water in sublation column, or minimize the back mixing of the aqueous phase in the sublation. [ABSTRACT FROM AUTHOR]

Administration of the anti-Thy1 antibody in rats induces reversible glomerulonephritis resembling human mesangiolytic and mesangioproliferative diseases. The purpose of the present study was to design a model of irreversible glomerulosclerosis, using the anti-Thy1 antibody injection after uninephrectomy, and examine it, focusing on apoptosis in the process of progressive sclerotic changes. Wistar rats were divided into three groups: one-kidney groups (group I and III) and a two-kidney group (group II). All groups were injected with the anti-Thy1 antibody (OX-7) at day 0, and group I and III were uninephrectomized at day−6. Only group III rats were given a half dose of OX-7 as compared with group I and II. Rats were killed for histological examinations at days 7, 14 and 30. In group I, progressive glomerular lesions, such as glomerular adhesion to Bowman's capsule, crescent formation, and collapse of capillary tufts were observed at days 14 and 30. No significant differences were observed in the pathological findings between group I and III. There was a significantly higher number of glomerular terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells in group I as compared to group II at days 7 and 14. Moreover, the glomerular expression of transforming growth factor-β, heparan sulfate proteoglycan and chondroitin sulfate proteoglycan significantly increased in group I as compared to group II at days 7 and 14. Progressive glomerulosclerosis can be induced in the rat by a single injection of the anti-Thy1 antibody after unilateral nephrectomy. It is suggested that apoptosis and extracellular matrix accumulation play an important role in the development of glomerulosclerosis. [ABSTRACT FROM AUTHOR]

The transcription factor OASIS gene, which encodes for a CREB/ATF family member, is specifically expressed in the salivary gland, the cartilage and the tooth germs of the mouse embryo. In the present study, the expression patterns were compared between OASIS mRNA and major vertebrate proteoglycans, which might be the downstream genes of OASIS in the tooth germs of mouse first mandibular molars, through in situ hybridization histochemistry. OASIS mRNA expression was observed in the inner enamel epithelium during the cap and bell stages (E14.5-E18.5) in the preodontoblasts during differentiation stage (E18.5-P0) and in the differentiating odontoblasts during the early secretory stage (P2.5-P4.5). Proteoglycans (versican, decorin, biglycan, glypican, syndecan-1, and syndecan-3) were expressed in the tooth germs in various patterns. Decorin, biglycan, syndecan-1 and syndecan-3 showed gene expressions overlapping with OASIS. Especially the expression pattern of decorin and syndecan-3 coincided temporally and spatially exactly with that of OASIS. These results suggest that the OASIS gene might be related to proteoglycan expression and may play an important role in the differentiation of the odontoblast and cells in inner enamel epithelium. [ABSTRACT FROM AUTHOR]