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A lightweight autonomous learning system for the course of software testing based on Android is developed according to the local teaching environment, and the system is fully applied on autonomous learning process outside class on campus. The system is designed on the architecture of SSH (Struts-Spring-Hibernate) which is based on J2EE for web server, and the functions of Course Information, Resource Management, Exercise, User Management and Online Discussion can be provided to client users by Android platform. Finally, further work such as how to add the function of online exam for subjective exam items in the system, how to add powerful function of micro video content editing for the management of course resource, and how to integrate this system into the local informational learning platform to complete the blended learning mode on SPOC (Small Private Online Course) are expected in the paper.

In recent years, the construction of MOOC (Massive Open Online Course) resources database has been paid more attention on MOOC research field. Based on the idea of integrable ware, MOOC elements are designed to form the corresponding MOOC learning knowledge points for some courses of software engineering major in a local university. They have the characteristics of openness, flexible and reusable. MOOC elements are fully applied in construction of the MOOC resources database on local campus for personalized learning effectively. The results show that teachers can select several different MOOC elements to form an important knowledge point for MOOC teaching process according to an actual course and reuse some existed MOOC elements to form another MOOC knowledge point for other courses. Different MOOC elements can be combined freely to form the related learning knowledge points for one course of software engineering major to stimulate and improve students’ interests in personalized learning. Finally, further work is put forward. Firstly, compatible supported conditions on software and hardware are to be created based on big data. Secondly, capacities on integrating and reusing of various types of MOOC resources by teachers should be improved. Thirdly, more reusable MOOC elements based on integrable ware for the courses of other majors should be designed and constructed for personalized learning.

Coding style is an important factor in measuring the program quality. The paper explores on the C program coding style of the program annotation writing, data declaration, program statement writing, and input/output design style from the perspective of software engineering. Good coding style plays an important role in improving the readability, testability and maintainability of the program.

OBJECTIVES: The NLRP3 inflammasome is a key regulator of innate immune responses, and its aberrant activation has been implicated in the pathogenesis of many complex diseases including multiple sclerosis, type 2 diabetes and atherosclerosis. Our study aimed to identify the food-borne exosome-like nanoparticles (ELNs) that inhibit NLRP3 inflammasome in macrophages. METHODS: ELNs from nine vegetables or fruits were purified using ultracentrifugation, incubated with bone-marrow derived macrophages, followed by the activation of NLRP3 inflammasome. After the dietary ELNs with strong inhibitory effects on inflammasome were identified, their roles in the inflammasome assembly and downstream pathways were further examined. RESULTS: We identified that ELNs from ginger rhizomes (G-ELNs) strongly inhibited NLRP3 inflammasome activation. We verified that G-ELNs were exosome-like nanoparticles containing biomolecules including RNAs, proteins, and lipids. The G-ELNs were taken up by macrophages. G-ELNs suppressed the downstream pathways of NLRP3 inflammasome activation including Casp1 auto-cleavage, interleukin (IL)-1 and IL-18 secretion, and pyroptotic cell death. G-ELNs blocked the assembling steps of NLRP3 inflammasome, but had no effects on protein levels of a key mediator of NLRP3 inflammasome NIMA-related kinase 7 (Nek7), or the inflammasome subunits NLRP3, ASC, and Casp1. CONCLUSIONS: Our findings identified G-ELNs as a new potent agent that blocks NLRP3 inflammasome assembly and activation. FUNDING SOURCES: This work was supported by the National Institutes of Health (NIH) 1P20GM104320 Nebraska Center Prevention of Obesity Diseases (NPOD) Seed Grant and Project Leader Grant, and the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) Hatch Project 1015948.

Technologies of the architecture on SSH(Struts-Spring-Hibernate), database interface access, and web data mining are used to analyse and design of a lightweight course website for software testing which is based on SPOC(Small Private Online Course) for blended teaching on campus. Functions of learning topics releasing on the course, organizing and coordinating learners' discussion to promote the learning process can be achieved through the website for teachers, and the website can also provide learners with selecting some social learning tools(BBS, QQ, WeChat) to complete online communication for the course learning. Finally, further work is expected in the paper. Firstly, the targeted and distinctive mobile learning resources and smart education mode should be constructed which is based on SPOC. Secondly, the visualized, diversified third-party platforms and tools in the course website should be integrated effectively which are enable learners to complete the process of online exercising or examining for some types of subjective testing items. Thirdly, how to ensure the reliability, toughness, running performance, safety, stability for the course website which is formed by cutting out some non-essential functions from existed MOOC(Massive Open Online Course) platforms, and improve the functions of multiple data statistics with web data mining technology and motivational observation for the website development.

As an important measure on quality assurance for web applications of website, web testing has been paid more attention in software testing recently. Based on the analysis of website and its application characteristics, from the view of affecting the quality of web applications, testing activities from the five aspects on functionality testing, performance testing, usability testing, compatibility testing and security testing are explored to assure the quality on web applications of website. Finally, further researches on comprehensive and adequate testing of the web service composition with some test techniques under the background of service-oriented technology and cloud computing technology, and how to combine exploratory testing with testing activities of functionality testing and usability testing effectively in web testing are expected in the paper.

Instructional software is a kind of software program or system, which reflects the teaching strategy according to the teaching objectives and teaching contents for the purpose on promoting teaching and learning by both computer technology and network technology. Firstly, the concept of instructional software, features and functions are introduced in the article. Secondly, making a detailed description on the current types of instructional software features for total eleven types, and discussing on main points on designing of instructional software for each type fully. Finally, an initial expectation on researches on directions of instructional software designing is given, which from three aspects on designing of teaching platform for SPOC(Small Private Online Course), designing of mobile learning resources, and the intelligence on designing of instructional software in the future.

On the basis of the feature analysis on development of online course from the perspective of software engineering, a testing framework of online course based on agile is designed firstly. The framework consists of four test cycles with iteration by test stages on preparing for testing, pre-testing, functionality testing and regression testing, and with a test process of acceptance testing at the end of four test cycles before product delivery. The evaluation on organization of the contents of chapter-section structure is also embodied in this framework. Secondly, the framework is fully applied to the agile testing project for an actual online course of "Software Engineering", experimental result shows that more bugs for types of structure of contents, usability, compatibility, installing, security, and navigability of the online course are detected in time and test result is noticeable. Finally, putting forward that some features and aspects on non-functionality testing through test automation together with effective exploratory testing method, and constructing an automated testing environment on cloud computing for big data processing will be the future research.

Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation.

Unliganded thyroid hormone receptor (TR) actively represses transcription via the nuclear receptor corepressor (N-CoR)/histone deacetylase 3 (HDAC3) complex. Although transcriptional activation by liganded receptors involves chromatin remodeling, the role of ATP-dependent remodeling in receptor-mediated repression is unknown. Here we report that SNF2H, the mammalian ISWI chromatin remodeling ATPase, is critical for repression of a genomically integrated, TR-regulated reporter gene. N-CoR and HDAC3 are both required for recruitment of SNF2H to the repressed gene. SNF2H does not interact directly with the N-CoR/HDAC3 complex, but binds to unacetylated histone H4 tails, suggesting that deacetylase activity of the corepressor complex is critical to SNF2H function. Indeed, HDAC3 as well as SNF2H are required for nucleosomal organization on the TR target gene. Consistent with these findings, reduction of SNF2H induces expression of an endogenous TR-regulated gene, dio1, in liver cells. Thus, although not apparent from studies of transiently transfected reporter genes, gene repression by TR involves the targeting of chromatin remodeling factors to repressed genes by the HDAC activity of nuclear receptor corepressors.

Nuclear receptor corepressors SMRT (silencing mediator of retinoid and thyroid receptors) and N-CoR (nuclear receptor corepressor) recruit histone deacetylase (HDAC) activity to targeted regions of chromatin. These corepressors contain a closely spaced pair of SANT motifs whose sequence and organization is highly conserved. The N-terminal SANT is a critical component of a deacetylase activation domain (DAD) that binds and activates HDAC3. Here, we show that the second SANT motif functions as part of a histone interaction domain (HID). The HID enhances repression by increasing the affinity of the DAD-HDAC3 enzyme for histone substrate. The two SANT motifs synergistically promote histone deacetylation and repression through unique functions. The HID contribution to repression is magnified by its ability to inhibit histone acetyltransferase enzyme activity. Remarkably, the SANT-containing HID preferentially binds to unacetylated histone tails. This implies that the SMRT HID participates in interpreting the histone code in a feed-forward mechanism that promotes and maintains histone deacetylation at genomic sites of SMRT recruitment.

Drosophila melanogaster display overt circadian rhythms in rest:activity behavior and eclosion. These rhythms have an endogenous period of approximately 24 hr and can adjust or "entrain" to environmental inputs such as light. Circadian rhythms depend upon a functioning molecular clock that includes the core clock genes period and timeless (reviewed in and ). Although we know that a clock in the lateral neurons (LNs) of the brain controls rest:activity rhythms, the cellular basis of eclosion rhythms is less well understood. We show that the LN clock is insufficient to drive eclosion rhythms. We establish that the prothoracic gland (PG), a tissue required for fly development, contains a functional clock at the time of eclosion. This clock is required for normal eclosion rhythms. However, both the PG clock function and eclosion rhythms require the presence of LNs. In addition, we demonstrate that pigment-dispersing factor (PDF), a neuropeptide secreted from LNs, is necessary for the PG clock and eclosion rhythms. Unlike other clocks in the fly periphery, the PG is similar to mammalian peripheral oscillators because it depends upon input, including PDF, from central pacemaker cells. This is the first report of a peripheral clock necessary for a circadian event.

As the derivation and innovation of MOOC (Massive Open Online Course), the development of SPOC (Small Private Online Course) platform which is based on MOOC idea can be better applied to the blended teaching of various courses in local universities in post-MOOC era. Based on the analysis of the current application of SPOC platform, from the view of technology in implementation, we explore the key technologies of identification on face recognition based on emotion calculation,course creating, editing and sharing, analysis of online learning behaviour and exercising or examining on subjective items for developing of a SPOC platform. Finally, further researches on how to construct on the targeted and distinctive mobile learning resources and smart education mode which is based on SPOC, how to provide formative assessment data and consciousness assessment data for learners accurately and function of data statistics and motivational observation that could be completed by teachers, how to cut some non-essential auxiliary functions of an existed MOOC platform for a certain local user group to form a flexible and usable SPOC platform with good expansibility are expected in the paper.

The acetylation of histone tails is a primary determinant of gene activity. Histone deacetylase 3 (HDAC3) requires the nuclear receptor corepressor SMRT for HDAC enzyme activity. Here we report that HDAC3 interacts with SMRT only after priming by cellular chaperones including the TCP-1 ring complex (TRiC), which is required for proper folding of HDAC3 in an ATP-dependent process. SMRT displaces TRiC from HDAC3, yielding an active HDAC enzyme. The SMRT–HDAC3 repression complex thus joins the VHL–elongin BC tumor suppression complex and the cyclin E–Cdk2 cell cycle regulation complex as critical cellular machines requiring TRiC for proper assembly and function. The strict control of HDAC3 activity underscores the cellular imperative that histone deacetylation occur only in targeted regions of the genome.

Inflammasomes are intracellular sensors that couple detection of pathogens and cellular stress to activation of Caspase-1, and consequent IL-1β and IL-18 maturation and pyroptotic cell death. Here, we show that the absent in melanoma 2 (AIM2) and nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasomes trigger Caspase-1-dependent mitochondrial damage. Caspase-1 activates multiple pathways to precipitate mitochondrial disassembly, resulting in mitochondrial reactive oxygen species (ROS) production, dissipation of mitochondrial membrane potential, mitochondrial permeabilization, and fragmentation of the mitochondrial network. Moreover, Caspase-1 inhibits mitophagy to amplify mitochondrial damage, mediated in part by cleavage of the key mitophagy regulator Parkin. In the absence of Parkin activity, increased mitochondrial damage augments pyroptosis, as indicated by enhanced plasma membrane permeabilization and release of danger-associated molecular patterns (DAMPs). Therefore, like other initiator caspases, Caspase-1 activation by inflammasomes results in mitochondrial damage.

A chlL-deletion mutant of Synechocystis sp. PCC 6803 designated as chlL- was unable to make significant amounts of chlorophyll in darkness. However, an apparent pseudorevertant has been generated spontaneously that can synthesize an increased amount of chlorophyll under light-activated heterotrophic growth conditions. Under these conditions, the chlorophyll content in this pseudorevertant was about 20% of that in the wild-type strain and about 4 times more than that in the original and in the recently recreated chlL-deletion mutant. This is paralleled by increased performance of dark-grown cells in terms of chlorophyll fluorescence induction and oxygen evolution rates in the pseudorevertant versus in the original mutant. PCR analysis confirmed that the chlL- -pseudorevertant mutant still lacked the chlL gene. These results imply that the light-independent chlorophyll biosynthesis pathway was partly recovered.

Inactivation of the chlL gene in Synechocystis sp. PCC 6803 resulted in negligible chlorophyll content when the mutant was grown in darkness. Upon phycocyanin excitation at 580 nm, the 77K fluorescence spectrum of dark-grown cells showed three peaks at 648 nm, 665 nm, and 685 nm, this last being the largest. This reflects the functional presence of major components of phycobilisomes, including phycocyanin, allophycocyanin, and the terminal emitter, and efficient energy transfer between these components. As expected, no fluorescence emission peaks corresponding to chlorophyll in the photosystems were observed. Intact phycobilisomes could be isolated from the dark-grown chlL-deletion mutant. However, the phycobilisomes had a lower efficiency of energy transfer than did those isolated from the light-grown mutant, probably because of a decreased phycobilisome stability in the absence of chlorophyll. Exposing the dark-grown chlL-deletion mutant to light triggered the biosynthesis of chlorophyll. For the first 6 h in the light, upon phycocyanin excitation at 580 nm, the 77K fluorescence emission spectrum of greening cells was identical to that of dark-grown cells that lacked significant amounts of chlorophyll. With increased chlorophyll synthesis, gradual energy transfer from phycobilisomes to the two photosystems can be demonstrated.

Sirt5, localized in the mitochondria, is a member of sirtuin family of NAD(+)-dependent deacetylases. Sirt5 was shown to deacetylate and activate carbamoyl phosphate synthase 1. Most recently, Sirt5 was reported to be the predominant protein desuccinylase and demalonylase in the mitochondria because the ablation of Sirt5 enhanced the global succinylation and malonylation of mitochondrial proteins, including many metabolic enzymes. In order to determine the physiological role of Sirt5 in metabolic homeostasis, we generated a germline Sirt5 deficient (Sirt5(-/-)) mouse model and performed a thorough metabolic characterization of this mouse line. Although a global protein hypersuccinylation and elevated serum ammonia during fasting were observed in our Sirt5(-/-) mouse model, Sirt5 deficiency did not lead to any overt metabolic abnormalities under either chow or high fat diet conditions. These observations suggest that Sirt5 is likely to be dispensable for the metabolic homeostasis under the basal conditions.

The NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) inflammasome mediates production of inflammatory mediators, such as IL-1β and IL-18, and as such is implicated in a variety of inflammatory processes, including infection, sepsis, autoinflammatory diseases, and metabolic diseases. The proximal steps in NLRP3 inflammasome activation are not well understood. Here we elucidate a critical role for Ca 2+ mobilization in activation of the NLRP3 inflammasome by multiple stimuli. We demonstrate that blocking Ca 2+ mobilization inhibits assembly and activation of the NLRP3 inflammasome complex, and that during ATP stimulation Ca 2+ signaling is pivotal in promoting mitochondrial damage. C/EPB homologous protein, a transcription factor that can modulate Ca 2+ release from the endoplasmic reticulum, amplifies NLRP3 inflammasome activation, thus linking endoplasmic reticulum stress to activation of the NLRP3 inflammasome. Our findings support a model for NLRP3 inflammasome activation by Ca 2+ -mediated mitochondrial damage.

Silent information regulator 2 (Sir2) proteins (sirtuins) are nicotinamide adenine dinucleotide-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1 to Sirt7. Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg 105) and tyrosine residue (Tyr 102) in the acyl pocket of Sirt5. Several mammalian proteins were identified with mass spectrometry to have succinyl or malonyl lysine modifications. Deletion of Sirt5 in mice appeared to increase the level of succinylation on carbamoyl phosphate synthase 1, which is a known target of Sirt5. Thus, protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo., postprint

The biological function of most proteins relies on reversible post-translational modifications, among which phosphorylation is most prominently studied and well recognized. Recently, a growing amount of evidence indicates that acetylation-deacetylation reactions, when applied to crucial mediators, can also robustly affect the function of target proteins and thereby have wide-ranging physiological impacts. Sirtuin 1 (SIRT1), which functions as a nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, deacetylates a wide variety of metabolic molecules in response to the cellular energy and redox status and as such causes significant changes in metabolic homeostasis. This review surveys the evidence for the emerging role of SIRT1-mediated deacetylation in the control of metabolic homeostasis.

International audience; Recently the function of the sirtuin family, named after their homology to the Saccharomyces cerevisiae gene silent information regulator 2 (Sir2), has received a lot of attention, as their beneficial impact on longevity was linked to their effects on metabolic control. All sirtuins require nicotinamide adenine dinucleotide (NAD(+)) for their deacetylase or ADP-ribosyl transferase activity, linking their function tightly to cellular energy levels. SIRT1, the founding member of the sirtuin family, modulates many aspects of glucose and lipid homeostasis in almost all key metabolic tissues. Other members including SIRT2, SIRT3, and SIRT4 are also implicated in various metabolic processes. Here, we review the recent data related to the role of sirtuins in the control of metabolic homeostasis and possible underlying molecular mechanisms.

Cells are frequently challenged by DNA double-strand breaks (DSB) that threaten their normal function and survival. In mammalian cells, the repair of DSBs is predominantly mediated by the DNA-dependent protein kinase (DNA-PK) complex. We unexpectedly found that the corepressor silencing mediator for retinoid and thyroid hormone receptor (SMRT) associates with the DNA-PK repair complex. The SMRT/histone deacetylase 3 complex is required for the transcriptional repressive property of the Ku70 subunit of the repair complex. Moreover, SMRT, but not the related Nuclear Receptor Corepressor, is required for cellular recovery from DNA DSBs induced by ionizing radiation or DNA damage–inducing drugs. Thus, the corepressor SMRT plays a novel and critical role in the cellular response to DSBs. (Cancer Res 2006; 66(18): 9316-22)

Ligands for nuclear receptors facilitate the exchange of co-repressors for coactivators, leading to chromatin modifications that favour the activation of gene transcription. Here, we show that the repressed state of an endogenous retinoic acid-regulated gene is quickly re-established after ligand removal. As expected, repression is characterized by recruitment of N-CoR/SMRT–HDAC3 (histone deacetylase 3) co-repressor complexes, leading to local histone hypoacetylation. The achievement of the repressed state involves the ordered deacetylation of lysines in H4 tails. This order is determined by the inherent substrate specificity of HDAC3, and unexpectedly predicts the binding preference of N-CoR/SMRT for submaximally acetylated H4 tails. The match between the specificity of acetyl-histone deacetylation by HDAC3 and the histone-binding preference of N-CoR/SMRT allows the co-repressor complex to stabilize and propagate repression of nuclear hormone receptor gene targets.

The identities of signal transducer proteins that integrate histone hypoacetylation and transcriptional repression are largely unknown. Here we demonstrate that THAP7, an uncharacterized member of the recently identified THAP (Thanatos-associated protein) family of proteins, is ubiquitously expressed, associates with chromatin, and represses transcription. THAP7 binds preferentially to hypoacetylated (un-, mono-, and diacetylated) histone H4 tails in vitro via its C-terminal 77 amino acids. Deletion of this domain, or treatment of cells with the histone deacetylase inhibitor TSA, which leads to histone hyperacetylation, partially disrupts THAP7/chromatin association in living cells. THAP7 coimmunoprecipitates with histone deacetylase 3 (HDAC3) and the nuclear hormone receptor corepressor (NCoR) and represses transcription as a Gal4 fusion protein. Chromatin immunoprecipitation assays demonstrate that these corepressors are recruited to promoters in a THAP7 dependent manner and promote histone H3 hypoacetylation. The conserved THAP domain is a key determinant for full HDAC3 association in vitro, and both the THAP domain and the histone interaction domain are important for the repressive properties of THAP7. Full repression mediated by THAP7 is also dependent on NCoR expression. We hypothesize that THAP7 is a dual function repressor protein that actively targets deacetylation of histone H3 necessary to establish transcriptional repression and functions as a signal transducer of the repressive mark of hypoacetylated histone H4. This is the first demonstration of the transcriptional regulatory properties of a human THAP domain protein, and a critical identification of a potential transducer of the repressive signal of hypoacetylated histone H4 in higher eukaryotes.

The AIM2 inflammasome is critical for host defense against certain intracellular bacteria and DNA viruses. It is a cytoplasmic complex consisting of the regulatory subunit AIM2, the adaptor ASC, and the effector subunit caspase-1. Stimulus dependent assembly of the complex activates the proteolytic activity of caspase-1, which is required for the processing and production of inflammatory cytokines IL-1β and IL-18. Here we demonstrate that mitochondrial damage is a consequence of activation of the AIM2 inflammasome. We address the underlying mechanisms, thus providing insight into regulation of a key inflammasome effector activity.

The nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase SIRT1 is a major metabolic regulator activated by energy stresses such as fasting or calorie restriction. SIRT1 activation during fasting not only relies on the increase in the NAD(+)/NADH ratio caused by energy deprivation but also involves an upregulation of SIRT1 mRNA and protein levels in various metabolic tissues. We demonstrate that SIRT1 expression is controlled systemically by the activation of the cyclic AMP response-element-binding protein upon low nutrient availability. Conversely, in the absence of energetic stress, the carbohydrate response-element-binding protein represses the expression of SIRT1. Altogether, these results demonstrate that SIRT1 expression is tightly controlled at the transcriptional level by nutrient availability and further underscore that SIRT1 is a crucial metabolic checkpoint connecting the energetic status with transcriptional programmes.