Redundant Actions Research Articles

RGS-Insensitive G Proteins as In Vivo Probes of RGS Function.

Guanine nucleotide-binding proteins of the inhibitory (Gi/o) class play critical physiological roles and the receptors that activate them are important therapeutic targets (e.g., mu opioid, serotonin 5HT1a, etc.). Gi/o proteins are negatively regulated by regulator of G protein signaling (RGS) proteins. The redundant actions of the 20 different RGS family members have made it difficult to establish their overall physiological role. A unique G protein mutation (G184S in Gαi/o) prevents RGS binding to the Gα subunit and blocks all RGS action at that particular Gα subunit. The robust phenotypes of mice expressing these RGS-insensitive (RGSi) mutant G proteins illustrate the profound action of RGS proteins in cardiovascular, metabolic, and central nervous system functions. Specifically, the enhanced Gαi2 signaling through the RGSi Gαi2(G184S) mutant knock-in mice shows protection against cardiac ischemia/reperfusion injury and potentiation of serotonin-mediated antidepressant actions. In contrast, the RGSi Gαo mutant knock-in produces enhanced mu-opioid receptor-mediated analgesia but also a seizure phenotype. These genetic models provide novel insights into potential therapeutic strategies related to RGS protein inhibitors and/or G protein subtype-biased agonists at particular GPCRs.

Landmark-Based Plan Distance Measures for Diverse Planning

Prior approaches to generating diverse plans in domain-independent planning seek out variations on plan structure such as actions or causal links used, or states entered. Measuring such syntactic differences between plans can be misleading because syntactically different plans can be semantically identical. We develop a landmark-based plan distance measure that captures semantic differences between plans.The landmark-based distance measure focuses on the disjunctive landmarks satisfied by each plan. We develop a simple algorithm for finding diverse plans that is based upon the LAMA planner. We illustrate that, in comparison with plan distance measures, landmark-based plan distance is not as susceptible to including irrelevant or redundant actions in plans to increase plan distance. Through extensive empirical evaluation, we find that high landmark distance between plans implies high action set distance, but not vice versa. Landmark-based plan distance overcomes some of the weaknesses of syntactic plan distance measures and can be used to find plan sets that are both landmark diverse and action set diverse.

Optimizing Plans through Analysis of Action Dependencies and Independencies

The problem of automated planning is known to be intractable in general. Moreover, it has been proven that in some cases finding an optimal solution is much harder than finding any solution. Existing techniques have to compromise between speed of the planning process and quality of solutions. For example, techniques based on greedy search often are able to obtain solutions quickly, but the quality of the solutions is usually low. Similarly, adding macro-operators to planning domains often enables planning speed-up, but solution sequences are typically longer. In this paper, we propose a method for optimizing plans with respect to their length, by post-planning analysis. The method is based on analyzing action dependencies and independencies by which we are able to identify redundant actions or non-optimal sub-plans. To evaluate the process we provide preliminary empirical evidence using benchmark domains.

When the transmission of culture is child's play.

BackgroundHumans frequently engage in arbitrary, conventional behavior whose primary purpose is to identify with cultural in-groups. The propensity for doing so is established early in human ontogeny as children become progressively enmeshed in their own cultural milieu. This is exemplified by their habitual replication of causally redundant actions shown to them by adults. Yet children seemingly ignore such actions shown to them by peers. How then does culture get transmitted intra-generationally? Here we suggest the answer might be ‘in play’.Principal FindingsUsing a diffusion chain design preschoolers first watched an adult retrieve a toy from a novel apparatus using a series of actions, some of which were obviously redundant. These children could then show another child how to open the apparatus, who in turn could show a third child. When the adult modeled the actions in a playful manner they were retained down to the third child at higher rates than when the adult seeded them in a functionally oriented way.ConclusionsOur results draw attention to the possibility that play might serve a critical function in the transmission of human culture by providing a mechanism for arbitrary ideas to spread between children.

Young children overimitate in third-party contexts

The exhibition of actions that are causally unnecessary to the outcomes with which they are associated is a core feature of human cultural behavior. To enter into the world(s) of their cultural in-group, children must learn to assimilate such unnecessary actions into their own behavioral repertoire. Past research has established the habitual tendency of children to adopt the redundant actions of adults demonstrated directly to them. Here we document how young children will do so even when such actions are modeled to a third person regardless of whether children are presented with the test apparatus by the demonstrating, and assumedly expert, adult or by the observing, and assumedly naive, adult (Experiment 1), whether or not children had opportunity to discover how the apparatus works prior to modeling (Experiment 1), and whether or not children’s attention was drawn to the demonstration while they were otherwise occupied (Experiment 2). These results emphasize human children’s readiness to acquire behavior that is in keeping with what others do, regardless of the apparent efficiency of the actions employed, and in so doing to participate in cultural learning.

Nucleus accumbens core mediates inhibition of redundant actions under learned no-reward situation

Nucleus accumbens core mediates inhibition of redundant actions under learned no-reward situation

Imitation in young children: When who gets copied is more important than what gets copied.

Unlike other animals, human children will copy all of an adult's goal-directed actions, including ones that are clearly unnecessary for achieving the demonstrated goal. Here we highlight how social affiliation is key to this species-specific behavior. Preschoolers watched 2 adults retrieve a toy from a novel apparatus. One adult included irrelevant actions in her demonstration; the other only used actions causally related to opening the apparatus. After both adults took turns demonstrating, 1 left the test room, and the remaining adult gave the apparatus to the child. Children reproduced the irrelevant actions only when given the apparatus by the adult who had demonstrated them, even though the departed adult's actions emphasized how unnecessary these redundant actions were. Our results highlight the specialized skills for participating in cultural groups that have evolved in humans and provide insight into why finding such high fidelity copying in other animals has proven elusive.

Determination of Carbohydrate‐Binding Preferences of Human Galectins with Carbohydrate Microarrays

Galectins are a class of carbohydrate-binding proteins named for their galactose-binding preference and are involved in a host of processes ranging from homeostasis of organisms to immune responses. As a first step towards correlating the carbohydrate-binding preferences of the different galectins with their biological functions, we determined carbohydrate recognition fine-specificities of galectins with the aid of carbohydrate microarrays. A focused set of oligosaccharides considered relevant to galectins was prepared by chemical synthesis. Structure-activity relationships for galectin-sugar interactions were determined, and these helped in the establishment of redundant and specific galectin actions by comparison of binding preferences. Distinct glycosylations on the basic lactosyl motifs proved to be key to galectin binding regulation--and therefore galectin action--as either high-affinity ligands are produced or binding is blocked. High-affinity ligands such as the blood group antigens that presumably mediate particular functions were identified.

A Study on the Optimization and Application of All Radial Truck Tire Building Process Technology

By analyzing the technology process of all steel radial truck tire building machine, the author finds that there is a big potential of improvement both in stitching effect and efficiency. A new kind of stitching and control device is designed to replace the original. The new device can realize the soft stitching of tire, which reduces redundant actions and thus optimizes the process and improves the stitching efficiency. It is found in tests that the optimized process reduces the blister defectives greatly. Both productivity and quality of tires are improved significantly. It shows a big economic benefit.

C-Cbl and Cbl-b Act Redundantly to Protect Osteoclasts from Apoptosis and to Displace HDAC6 from β-Tubulin, Stabilizing Microtubules and Podosomes

c-Cbl and Cbl-b are highly conserved adaptor proteins that participate in integrin signaling, regulating cytoskeletal organization, motility, and bone resorption. Deletion of both c-Cbl and Cbl-b in mice leads to embryonic lethality, indicating that the two proteins perform essential redundant functions. To examine the redundant actions of c-Cbl and Cbl-b in osteoclasts, we depleted c-Cbl in Cbl-b(-/-) osteoclasts by using a short hairpin RNA. Depleting both Cbl proteins disrupted both the podosome belt and the microtubule network and decreased bone-resorbing activity. Stabilizing the microtubules with paclitaxel or inhibiting histone deacetylase 6 (HDAC6), which destabilizes microtubules by deacetylating beta-tubulin, protected both the microtubule network and the podosome belt. Examination of the mechanism involved demonstrated that the conserved four-helix bundle of c-Cbl's tyrosine kinase binding domain bound to beta-tubulin, and both c-Cbl and Cbl-b displaced HDAC6. In addition to the effects on microtubules and the podosome belt, depleting both Cbls significantly increased the levels of the proapoptotic protein Bim and apoptosis relative to the levels induced by eliminating either protein alone. Thus, both c-Cbl and Cbl-b promote bone resorption via the stabilization of microtubules, allowing the formation of the podosome belt in osteoclasts, and by promoting osteoclast survival.

Phytochrome A is an irradiance‐dependent red light sensor

Plants perceive red (R) and far-red (FR) light signals using the phytochrome family of photoreceptors. In Arabidopsis thaliana, five phytochromes (phyA-phyE) have been identified and characterized. Unlike other family members, phyA is subject to rapid light-induced proteolytic degradation and so accumulates to relatively high levels in dark-grown seedlings. The insensitivity of phyA mutant seedlings to prolonged FR and wild-type appearance in R has led to suggestions that phyA functions predominantly as an FR sensor during the early stages of seedling establishment. The majority of published photomorphogenesis experiments have, however, used <50 micromol m(-2) sec(-1) of R when characterizing phytochrome functions. Here we reveal considerable phyA activity in R at higher (>160 micromol m(-2) sec(-1)) photon irradiances. Under these conditions, plant architecture was observed to be largely regulated by the redundant actions of phytochromes A, B and D. Moreover, quadruple phyBphyCphyDphyE mutants containing only functional phyA displayed R-mediated de-etiolation and survived to flowering. The enhanced activity of phyA in continuous R (Rc) of high photon irradiance correlates with retarded degradation of the endogenous protein in wild-type plants and prolonged epifluorescence of nuclear-localized phyA:YFP in transgenic lines. Such observations suggest irradiance-dependent 'photoprotection' of nuclear phyA in R, providing a possible explanation for the increased activity observed. The discovery that phyA can function as an effective irradiance sensor, even in light environments that establish a high Pfr concentration, raises the possibility that phyA may contribute significantly to the regulation of growth and development in daylight-grown plants.

Phosphorylation of MCM4 at Sites Inactivating DNA Helicase Activity of the MCM4-MCM6-MCM7 Complex during Epstein-Barr Virus Productive Replication

Induction of Epstein-Barr virus (EBV) lytic replication blocks chromosomal DNA replication notwithstanding an S-phase-like cellular environment with high cyclin-dependent kinase (CDK) activity. We report here that the phosphorylated form of MCM4, a subunit of the MCM complex essential for chromosomal DNA replication, increases with progression of lytic replication, Thr-19 and Thr-110 being CDK2/CDK1 targets whose phosphorylation inactivates MCM4-MCM6-MCM7 (MCM4-6-7) complex-associated DNA helicase. Expression of EBV-encoded protein kinase (EBV-PK) in HeLa cells caused phosphorylation of these sites on MCM4, leading to cell growth arrest. In vitro, the sites of MCM4 of the MCM4-6-7 hexamer were confirmed to be phosphorylated with EBV-PK, with the same loss of helicase activity as with CDK2/cyclin A. Introducing mutations in the N-terminal six Ser and Thr residues of MCM4 reduced the inhibition by CDK2/cyclin A, while EBV-PK inhibited the helicase activities of both wild-type and mutant MCM4-6-7 hexamers, probably since EBV-PK can phosphorylate MCM6 and another site(s) of MCM4 in addition to the N-terminal residues. Therefore, phosphorylation of the MCM complex by redundant actions of CDK and EBV-PK during lytic replication might provide one mechanism to block chromosomal DNA replication in the infected cells through inactivation of DNA unwinding by the MCM4-6-7 complex.

Short-term delay of Fas-stimulated apoptosis by GM-CSF as a result of temporary suppression of FADD recruitment in neutrophils: evidence implicating phosphatidylinositol 3-kinase and MEK1-ERK1/2 pathways downstream of classical protein kinase C.

Granulocyte/macrophage colony-stimulating factor (GM-CSF) inhibits Fas-induced apoptosis of neutrophils. However, the exact step in the apoptotic pathway blocked by GM-CSF remained unclear. Here, we found that pretreatment of neutrophils with GM-CSF inhibits the recruitment of Fas-associated protein with death domain (FADD) to Fas, abolishing the formation of the death-inducing signaling complex required for Fas-induced apoptosis. Two-dimensional electrophoresis revealed that GM-CSF modifies the ratio of FADD subspecies. These GM-CSF-triggered changes were abrogated, and Fas-induced apoptosis was restored by an inhibitor of classical protein kinase C (PKC), Go6976, and by the combination of a phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002, and an inhibitor of mitogen-activated protein kinase kinase (MEK)1, PD98059. Go6976 blocked GM-CSF-elicited phosphorylation of Akt/PKB and extracellular signal-regulated kinase (ERK)1/2. These results indicated that GM-CSF suppresses Fas-induced neutrophil apoptosis by inhibiting FADD binding to Fas, through redundant actions of PI-3K and MEK1-ERK1/2 pathways downstream of classical PKC.

The operators' non-compliance behavior to conduct emergency operating procedures—comparing with the work experience and the complexity of procedural steps

Abstract Many kinds of procedures have been used to reduce the operators' workload throughout various industries, such as in the aviation, the chemical and the nuclear industry. It is remarkable that, however, significant portion of accidents or incidents was caused by procedure related human error due to non-compliance of procedures. In this study, to investigate the operators' non-compliance behavior, emergency-training records were collected using a full scope simulator. And three types of the operators' behavior (such as strict adherence, skipping redundant actions and modifying action sequences) observed from collected emergency training records were compared with both their work experience and the complexity of procedural steps. As the results, three remarkable relationships are obtained. They are: (1) the operators who have an intermediate work experience seem to frequently adopt non-compliance behavior to conduct the procedural steps, (2) the operators seem to frequently adopt non-compliance behavior to conduct the procedural steps that have an intermediate procedural complexity, and (3) the senior reactor operators seem to accommodate their non-compliance behavior based on the complexity of procedural steps. Therefore, it is expected that these relationships can be used as meaningful clues not only to scrutinize the reason for non-compliance behavior but also to suggest appropriate remedies for the reduction of non-compliance behavior that can result in procedure related human error.

TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase.

EGF family growth factors, including transforming growth factor-alpha (TGFalpha), amphiregulin (AR), and heparin-binding EGF (HB-EGF), are invariably expressed as transmembrane precursors that are cleaved at one or more sites in the extracellular domain to release soluble growth factor. Considerable attention has focused on the identification of proteases responsible for these processing events. We previously implicated tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) in the generation of soluble TGFalpha from its transmembrane precursor, proTGFalpha. Here, we review our findings that primary keratinocytes from Tace(deltaZn/deltaZn) mice, which express a nonfunctional TACE, released dramatically lower levels of soluble TGFalpha compared to their normal counterparts, even though TGFalpha mRNA and cell-associated protein levels were similar in the two cell populations. Restoration of TACE activity in Tace(deltaZn/deltaZn) cells increased shedding of TGFalpha species, including the mature, 6-kDa protein. Further, exogenous TACE enzyme accurately cleaved the N-terminal processing site of proTGFalpha in cell lysates, as well as both physiologic sites of a soluble proTGFalpha ectodomain. TACE also accurately cleaved peptide substrates corresponding to the processing sites of several additional EGF family members, and restoration of TACE activity enhanced the shedding of soluble AR and HB-EGF proteins from Tace(deltaZn/deltaZn) cells. Finally, reduction of functional TACE gene dosage greatly exacerbated the open-eye defect of Egfr(wa-2/wa-2) newborns, which is regulated by redundant actions of several EGF family ligands. The implications of these results for the biology of the EGF family and TACE are discussed.

The expression of the non-receptor tyrosine kinases Arg and c-abl is differently modulated in B lymphoid cells at different stages of differentiation

The products of the human ARG gene and the human ABL gene characterize the Abelson family of non-receptor tyrosine protein kinases. Both genes are ubiquitously expressed. The interactions of these two similar protein kinases are still not well known, although it has been suggested that they could cooperate, with redundant actions, to provide intracellular signals in the cells. Lymphopenia occurs in mice with homozygous disruption of c-abl, indicating that in certain tissues Arg is unable to substitute c-abl functions. In B and T lymphoid cell lines at different stages of differentiation, we studied, by a reverse transcriptase-competitive polymerase chain reaction and Western blotting, Arg and c-abl in order to evaluate whether the expression pattern of the two genes could give insight as to why they do not exhibit overlapping roles in lymphocytes and whether the product levels of the two genes are related to lymphoid differentiation. The data showed that their expression is differently modified in lymphoid B cell lines. The highest Arg transcript and protein levels are in the mature B cells.

Matrix Metalloproteinases

Matrix metalloproteinases (MMPs) contribute to cell migration and cell proliferation by degrading the extracellular matrix (ECM) and by releasing growth factors bound up in the ECM. The actions of MMPs are held in check by a class of proteins called tissue inhibitors of metalloproteinases (TIMPs). Vu and Werb review the physiological functions of MMP in development and in cell regulation and cover in more depth the topics ranging from bone and mammary development to zygotic implantation and wound healing. MMPs may act independently or in concert with other MMPs that share some redundant actions. Thus, the authors point out, the elucidation of the functions that each MMP has within organismic development and, more narrowly, organ development, have only been revealed through difficult work. Similarly, what the favored substrate is for each MMP is largely unknown. Vu, T.H., and Werb, Z. (2000) Matrix metalloproteinases: Effectors of development and normal physiology. Genes Dev . 14 : 2123-2133. [Full Text]

The role of IL-2 in allograft rejection--a lesson learned from experimental work.

The role of IL-2 in allograft rejection--a lesson learned from experimental work.

Trichome cell growth in Arabidopsis thaliana can be derepressed by mutations in at least five genes.

Leaf trichomes in Arabidopsis are unicellular epidermal hairs with a branched morphology. They undergo successive endoreduplication rounds early during cell morphogenesis. Mutations affecting trichome nuclear DNA content, such as triptychon or glabra3, alter trichome branching. We isolated new mutants with supernumerary trichome branches, which fall into three unlinked complementation groups: KAKTUS and the novel loci, POLYCHOME and RASTAFARI. They map to chromosomes IV, II, and V, respectively. The trichomes of these mutants presented an increased DNA content, although to a variable extent. The spindly-5 mutant, which displays a constitutive gibberellin response, also produces overbranched trichomes containing more nuclear DNA. We analyzed genetic interactions using double mutants and propose that two independent pathways, defined by SPINDLY and TRIPTYCHON, act to limit trichome growth. KAKTUS and POLYCHOME might have redundant actions mediating gibberellin control via SPINDLY. The overall leaf polysomaty was not notably affected by these mutations, suggesting that they affect the control of DNA synthesis in a tissue- or cell type-specific manner. Wild-type tetraploids also produce overbranched trichomes; they displayed a shifted polysomaty in trichomes and in the whole leaf, suggesting a developmental program controlling DNA increases via the counting of endoreduplication rounds.

Magic templates: a spellbinding approach to logic programs

We consider a bottom-up query-evaluation scheme in which facts of relations are allowed to have nonground terms. The magic-sets query- rewriting technique is generalized to allow arguments of predicates to be treated as bound even though the rules do not provide ground bindings for those arguments. In particular, we regard as “bound” any argument containing a function symbol or a variable that appears more than once in the argument list. Generalized “magic” predicates are thus defined to compute the set of all goals reached in a top-down exploration of the rules, starting from a given query goal; these goals are not facts of constants as in previous versions of the magic-sets algorithm. The magic predicates are then used to restrict a bottom-up evaluation of the rules so that there are no redundant actions; that is, every step of the bottom-up computation must be performed by any algorithm that uses the same sideways information-passing strategy (sips). The price paid, compared to previous versions of Magic Sets, is that we must store relations with nonground facts, and we must perform unifications, rather than equijoins, when evaluating the rules bottom-up. The method is applicable to general Horn-clause logic programs.