Functional Duality Research Articles

Probabilities, beliefs, and dual processing: the paradigm shift in the psychology of reasoning

In recent years, the psychology of reasoning has been undergoing a paradigm shift, with general Bayesian, probabilistic approaches replacing the older, much more restricted binary logic paradigm. At the same time, dual processing theories have been gaining influence. We argue that these developments should be integrated and moreover that such integration is already underway. The new reasoning paradigm should be grounded in dual processing for its algorithmic level of analysis just as it uses Bayesian theory for its computational level of analysis. Moreover, we propose that, within the new paradigm, these levels of analysis reflect on each other. Bayesianism suggests a specific theoretical understanding of dual processing. Just as importantly, the duality in processing carries over to duality in function; although both types of processes compute degrees of belief, they generate different functions.

Identification of novel microRNAs in Hevea brasiliensisand computational prediction of their targets

BackgroundPlants respond to external stimuli through fine regulation of gene expression partially ensured by small RNAs. Of these, microRNAs (miRNAs) play a crucial role. They negatively regulate gene expression by targeting the cleavage or translational inhibition of target messenger RNAs (mRNAs). In Hevea brasiliensis, environmental and harvesting stresses are known to affect natural rubber production. This study set out to identify abiotic stress-related miRNAs in Hevea using next-generation sequencing and bioinformatic analysis.ResultsDeep sequencing of small RNAs was carried out on plantlets subjected to severe abiotic stress using the Solexa technique. By combining the LeARN pipeline, data from the Plant microRNA database (PMRD) and Hevea EST sequences, we identified 48 conserved miRNA families already characterized in other plant species, and 10 putatively novel miRNA families. The results showed the most abundant size for miRNAs to be 24 nucleotides, except for seven families. Several MIR genes produced both 20-22 nucleotides and 23-27 nucleotides. The two miRNA class sizes were detected for both conserved and putative novel miRNA families, suggesting their functional duality. The EST databases were scanned with conserved and novel miRNA sequences. MiRNA targets were computationally predicted and analysed. The predicted targets involved in "responses to stimuli" and to "antioxidant" and "transcription activities" are presented.ConclusionsDeep sequencing of small RNAs combined with transcriptomic data is a powerful tool for identifying conserved and novel miRNAs when the complete genome is not yet available. Our study provided additional information for evolutionary studies and revealed potentially specific regulation of the control of redox status in Hevea.

The dual behavior of heat shock protein 70 and asymmetric dimethylarginine in relation to serum CRP levels in type 2 diabetes

BackgroundExperimental evidence suggests that heat shock proteins (HSP) and asymmetric dimethylarginine (ADMA) are induced in the state of chronic inflammation and stress conditions. They are both inhibitors of nitric oxide synthase (NOS). The aim of this study was to evaluate the correlation between ADMA and HSP70, in patients with type 2 diabetes with respect to serum levels of C reactive protein (CRP). MethodsWe quantified serum HSP70, ADMA and CRP in 80 newly-diagnosed patients with type 2 diabetes plus 80 age-, sex and BMI-matched healthy controls. The patients and controls were also stratified into groups of high and low CRP levels (cut-point: 2.5mg/ml). ResultsPatients with type 2 diabetes had significantly higher serum HSP70 (0.52 [0.51–0.66] vs. 0.27 [0.26–0.36], p<0.001), ADMA (0.86 [0.81–0.92] vs. 0.72 [0.71–0.85], p<0.05) and CRP (2.9 [1.7–3.4] vs. 1.6[1.2–2.3], p<0.05) compared with healthy controls. Serum HSP70 and ADMA levels were significantly correlated in patients with high CRP levels (r=0.89, p<0.01), whereas there were no correlation in patients with low CRP (r=−0.37, p=0.07) and controls. This correlation was significant (r=0.77, p<0.001) in patients with high CRP and also in patients with low CRP levels (r=−0.51, p<0.05), after multiple adjustments for LDL and HDL levels. DiscussionWe showed that, in a state of high inflammation; serum levels of ADMA parallel the HSP70 levels. However in low inflammation, they are negatively correlated. The duality in HSP70 and ADMA correlation may be related to the duality of NOS function in low and high CRP levels.

Functional Duality between Distributed Source Coding and Broadcast Channel Coding in the Case of Correlated Messages

In this letter, functional duality between distributed source coding (DSC) with correlated messages and broadcast channel coding (BCC) with correlated messages is considered. It is shown that under certain conditions, for a given DSC problem with correlated messages, a functional dual BCC problem with correlated messages can be obtained, and vice versa. That is, the optimal encoder-decoder mappings for one problem become the optimal decoder-encoder mappings for the dual problem. Furthermore, the correlation structure of the messages in the two dual problems and the source distortion and channel cost measure for this duality are specified.

Functional Duality of Astrocytes in Myelination

Astrocytes undergo major phenotypic changes in response to injury and disease that directly influence repair in the CNS, but the mechanisms involved are poorly understood. Previously, we have shown that neurosphere-derived rat astrocytes plated on poly-L-lysine (PLL-astrocytes) support myelination in dissociated rat spinal cord cultures (myelinating cultures). It is hypothesized that astrocyte reactivity can affect myelination, so we have exploited this culture system to ascertain how two distinct astrocyte phenotypes influence myelination. Astrocytes plated on tenascin C (TnC-astrocytes), a method to induce quiescence, resulted in less myelinated fibers in the myelinating cultures when compared with PLL-astrocytes. In contrast, treatment of myelinating cultures plated on PLL-astrocytes with ciliary neurotrophic factor (CNTF), a cytokine known to induce an activated astrocyte phenotype, promoted myelination. CNTF could also reverse the effect of quiescent astrocytes on myelination. A combination of microarray gene expression analysis and quantitative real-time PCR identified CXCL10 as a potential candidate for the reduction in myelination in cultures on TnC-astrocytes. The effect of TnC-astrocytes on myelination was eliminated by neutralizing CXCL10 antibodies. Conversely, CXCL10 protein inhibited myelination on PLL-astrocytes. Furthermore, CXCL10 treatment of purified oligodendrocyte precursor cells did not affect proliferation, differentiation, or process extension compared with untreated controls, suggesting a role in glial/axonal ensheathment. These data demonstrate a direct correlation of astrocyte phenotypes with their ability to support myelination. This observation has important implications with respect to the development of therapeutic strategies to promote CNS remyelination in demyelinating diseases.

Comments on: Stability in linear optimization and related topics. A personal tour

Linear semi-infinite optimization problems (LSIPs) arise in a large number of applications, including functional approximation, robust optimization, optimal control, and duality theory. Whereas in many applications the index set of these inequality constraints is a compact subset of some Euclidean space, the presented survey takes an even more general point of view, where the index set is not equipped with any kind of structure. For the numerical treatment of an optimization problem it is crucial that the problem is stable under perturbations of its defining data. Different stability properties lead to a list of notions for ‘good behavior’ of an LSIP, including semicontinuity properties of feasible and optimal point mappings, different types of ill-posedness, distance to ill-posedness, as well as Lipschitz and metric regularity properties. Marco Lopez and his coauthors have studied these qualitative and quantitative notions extensively during the last fifteen years. Their remarkable results are compiled in the present, comprehensive survey about stability in linear semi-infinite optimization. Since the main questions in the framework of this survey appear to be answered, I would like to take this opportunity and suggest to slightly extend this setting. In fact, while the index set T itself is assumed to be fixed in the present approach, there are at least three possible ways to study LSIPs with parametric index sets.

The Dual Role of Sirtuins in Cancer

Among the greatest challenges facing organisms is that of detecting and effectively responding to life-threatening environmental changes that are intimately associated with metabolic fluctuations and certain forms of stress. These conditions have been linked to the onset of many human pathologies, including cancer. Over the past decade, members of the Sir2 family, or sirtuins, have been described as major players in sensing and coordinating stress response. Evidence has imputed mammalian sirtuins in carcinogenesis, although the mechanisms involved seem to be more diverse and complex than previously anticipated. Some sirtuins, such as SirT2 and SirT6, seem to work as tumor suppressors, but others, such as SirT1, are apparently bifunctional: operating as both tumor suppressors and oncogenic factors depending on the context and the study conditions. The mechanisms underlying these apparently contradictory activities are not well understood, although recent findings suggest that they might actually be two sides of the same coin. In this review, the authors summarize current knowledge on the functional implications of sirtuins in cancer and discuss possible explanations for their functional duality.

Ribosome Synthesis-Unrelated Functions of the Preribosomal Factor Rrp12 in Cell Cycle Progression and the DNA Damage Response

Given the high metabolic cost required to generate ribosomes, it has been assumed that proteins involved in ribosome synthesis might establish functional cross talk with other intracellular processes to efficiently couple ribosome production and cell growth. However, such interconnections have remained elusive due to the difficulty in separating the intra- and extraribosomal roles of ribosome biogenesis factors. Using a yeast functional screen, I have discovered that Rrp12, a conserved protein involved in ribosome maturation and export, plays roles in the cell cycle and the DNA damage response. These results indicate that Rrp12 participates in a karyopherin Kap121-dependent import route that is crucial for nuclear sequestration of ribonucleotide reductase subunits and, thereby, ensures the proper kinetics of deoxyribonucleotide production during the cell cycle. Within this route, Rrp12 acts as a cofactor important for the full functionality of Kap121. This activity is mechanistically different from the known roles of Rrp12 in ribosome biogenesis. I propose that the functional duality of Rrp12 may couple the control of ribosome production to the regulation of other cellular processes during cell cycle progression.

Homodimerization of the Src Homology 3 Domain of the Calcium Channel β-Subunit Drives Dynamin-dependent Endocytosis

Voltage-dependent calcium channels constitute the main entry pathway for calcium into excitable cells. They are heteromultimers formed by an α(1) pore-forming subunit (Ca(V)α(1)) and accessory subunits. To achieve a precise coordination of calcium signals, the expression and activity of these channels is tightly controlled. The accessory β-subunit (Ca(V)β), a membrane associated guanylate kinase containing one guanylate kinase (β-GK) and one Src homology 3 (β-SH3) domain, has antagonistic effects on calcium currents by regulating different aspects of channel function. Although β-GK binds to a conserved site within the α(1)-pore-forming subunit and facilitates channel opening, β-SH3 binds to dynamin and promotes endocytosis. Here, we investigated the molecular switch underlying the functional duality of this modular protein. We show that β-SH3 homodimerizes through a single disulfide bond. Substitution of the only cysteine residue abolishes dimerization and impairs internalization of L-type Ca(V)1.2 channels expressed in Xenopus oocytes while preserving dynamin binding. Covalent linkage of the β-SH3 dimerization-deficient mutant yields a concatamer that binds to dynamin and restores endocytosis. Moreover, using FRET analysis, we show in living cells that Ca(V)β form oligomers and that this interaction is reduced by Ca(V)α(1). Association of Ca(V)β with a polypeptide encoding the binding motif in Ca(V)α(1) inhibited endocytosis. Together, these findings reveal that β-SH3 dimerization is crucial for endocytosis and suggest that channel activation and internalization are two mutually exclusive functions of Ca(V)β. We propose that a change in the oligomeric state of Ca(V)β is the functional switch between channel activator and channel internalizer.

FoxO1 represses mTOR dependent T-bet expression to facilitate CD8+ T cell memory (46.21)

Abstract The ability of mTOR to regulate T-bet expression is central to its role in CD8+ T cell differentiation for type 1 effector functions. However, the mechanisms underpinning mTOR mediated T-bet expression are not completely understood. We demonstrate that instructional programming of naïve CD8+ (OT-1) T cells for mTOR and T-bet dependent type I effector functions, induces Akt dependent FoxO1 phosphorylation; leading to its nuclear exclusion and loss in expression of its target genes; KLF2 and CD62L. Inhibition of mTOR by rapamycin blocks FoxO1 phosphorylation, whereby increasing its expression, nuclear translocation for enhanced expression of KLF2, CD62L and for transitioning type 1 CD8+ effector to memory precursor cells. The rapamycin mediated FoxO1 expression is required to inhibit T-bet expression (mRNA, protein), switching the transcriptional profile of OT-1 cells from T-bet to Eomesodermin. Furthermore, transgenic Myr-Akt (active) or FoxO1 knockdown (siRNA) or T-bet re-expression restores type 1 effector functions in rapamycin treated FoxO1+ memory precursor OT-1 cells, indicating the essential role FoxO1 mediated T-bet repression for memory. These results reveal a novel role for FoxO1 in regulating T-bet dependent type 1effector maturation and identify duality of FoxO1 functions in regulating CD8+ T cell memory.

Fatty acid modification of Wnt1 and Wnt3a at serine is prerequisite for lipidation at cysteine and is essential for Wnt signalling

The Wnt family of proteins is a group of extracellular signalling molecules that regulate cell-fate decisions in developing and adult tissues. It is presumed that all 19 mammalian Wnt family members contain two types of post-translational modification: the covalent attachment of fatty acids at two distinct positions, and the N-glycosylation of multiple asparagines. We examined how these modifications contribute to the secretion, extracellular movement and signalling activity of mouse Wnt1 and Wnt3a ligands. We revealed that O-linked acylation of serine is required for the subsequent S-palmitoylation of cysteine. As such, mutant proteins that lack the crucial serine residue are not lipidated. Interestingly, although double-acylation of Wnt1 was indispensable for signalling in mammalian cells, in Xenopus embryos the S-palmitoyl-deficient form retained the signalling activity. In the case of Wnt3a, the functional duality of the attached acyls was less prominent, since the ligand lacking S-linked palmitate was still capable of signalling in various cellular contexts. Finally, we show that the signalling competency of both Wnt1 and Wnt3a is related to their ability to associate with the extracellular matrix.

GABA: ¿dualidad funcional? Transición durante el neurodesarrollo

Gamma-aminobutyric acid (GABA) is the most important inhibitory-type neurotransmitter and its actions are mediated by ionotropic (GABA(A)) and metabotropic (GABA(B)) type receptors, which are widely distributed throughout the tissue of the central nervous system. To review the structure of GABA receptors and their involvement in physiological processes in the central nervous system. The study addresses the structure and diversity of the GABA receptors, especially during neurodevelopment, and reference is made to the excitatory and inhibitory nature of GABAergic transmission, where the participation of the cotransporters NKCC1 and KCC2 plays a key role in this functional duality in the transition from an embryonic to a post-natal state. Likewise, the interest in GABA receptors as a pharmacological target for clinical use is also discussed. This is manifested by the presence of under-explored allosteric modulation sites in the aforementioned complex-receptor. The physiological and pharmacological knowledge of the great diversity of subunits that make up a particular subtype of GABA receptor, as well as the correct expression in time and space in order to ensure the viability of the organism, promise to be the answer to long-time severe disorders like epilepsy or drug addiction, and such complex ones as neurodevelopment.

Asymptotic strong duality

Given a nonconvex and nonsmooth optimization problem, we define a family of ``perturbed'' Lagrangians, which induce well-behaved approximations of the dual problem. Our family of approximated problems is said to verify {\em strong asymptotic duality} when the optimal dual values of the perturbed problems approach the primal optimal value. Our perturbed Lagrangians can have the same order of smoothness as the functions of the original problem, a property not shared by the classical (unperturbed) augmented Lagrangian. Therefore our proposed scheme allows the use of efficient numerical methods for solving the perturbed dual problems. We establish general conditions under which strong asymptotic duality holds, and we relate the latter with both strong duality and lower semicontinuity of the perturbation function. We illustrate our perturbed duality scheme with two important examples: Constrained Nonsmooth Optimization and Nonlinear Semidefinite programming.

Oligomeric Coiled-Coil Adhesin YadA Is a Double-Edged Sword

Yersinia adhesin A (YadA) is an essential virulence factor for the food-borne pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis. Suprisingly, it is a pseudogene in Yersinia pestis. Even more intriguing, the introduction of a functional yadA gene in Y. pestis EV76 was shown to correlate with a decrease in virulence in a mouse model. Here, we report that wild type (wt) Y. enterocolitica E40, as well as YadA-deprived E40 induced the synthesis of neutrophil extracellular traps (NETs) upon contact with neutrophils, but only YadA-expressing Y. enterocolitica adhered to NETs and were killed. As binding seemed to be a prerequisite for killing, we searched for YadA-binding substrates and detected the presence of collagen within NETs. E40 bacteria expressing V98D,N99A mutant YadA with a severely reduced ability to bind collagen were found to be more resistant to killing, suggesting that collagen binding contributes significantly to sensitivity to NETs. Wt Y. pestis EV76 were resistant to killing by NETs, while recombinant EV76 expressing YadA from either Y. pseudotuberculosis or Y. enterocolitica were sensitive to killing by NETs, outlining the importance of YadA for susceptibility to NET-dependent killing. Recombinant EV76 endowed with YadA from Y. enterocolitica were also less virulent for the mouse than wt EV76, as shown before. In addition, EV76 carrying wt YadA were less virulent for the mouse than EV76 expressing YadAV98D,N99A. The observation that YadA makes Yersinia sensitive to NETs provides an explanation as for why evolution selected for the inactivation of yadA in the flea-borne Y. pestis and clarifies an old enigma. Since YadA imposes the same cost to the food-borne Yersinia but was nevertheless conserved by evolution, this observation also illustrates the duality of some virulence functions.

Correction to “On Functional Duality in Multiuser Source and Channel Coding Problems Having One-Sided Collaboration” [Jul 06 2986-3002

In the above titled paper (ibid., vol. 52, no. 7, pp. 2986-3002, Jul. 06), there is an error on line 8 in the first paragraph on the left column on page 2992 regarding broadcast channels. The equation is not correct and thus the argument given in the rest of the paragraph is not valid. A correct argument is presented here.

Androgen receptor signaling and mutations in prostate cancer.

Normal and neoplastic growth of the prostate gland are dependent on androgen receptor (AR) expression and function. Androgenic activation of the AR, in association with its coregulatory factors, is the classical pathway that leads to transcriptional activity of AR target genes. Alternatively, cytoplasmic signaling crosstalk of AR by growth factors, neurotrophic peptides, cytokines or nonandrogenic hormones may have important roles in prostate carcinogenesis and in metastatic or androgen-independent (AI) progression of the disease. In addition, cross-modulation by various nuclear transcription factors acting through basal transcriptional machinery could positively or negatively affect the AR or AR target genes expression and activity. Androgen ablation leads to an initial favorable response in a significant number of patients; however, almost invariably patients relapse with an aggressive form of the disease known as castration-resistant or hormone-refractory prostate cancer (PCa). Understanding critical molecular events that lead PCa cells to resist androgen-deprivation therapy is essential in developing successful treatments for hormone-refractory disease. In a significant number of hormone-refractory patients, the AR is overexpressed, mutated or genomically amplified. These genetic alterations maintain an active presence for a highly sensitive AR, which is responsive to androgens, antiandrogens or nonandrogenic hormones and collectively confer a selective growth advantage to PCa cells. This review provides a brief synopsis of the AR structure, AR coregulators, posttranslational modifications of AR, duality of AR function in prostate epithelial and stromal cells, AR-dependent signaling, genetic changes in the form of somatic and germline mutations and their known functional significance in PCa cells and tissues.

Orlicz–Hardy spaces associated to operators satisfying bounded [formula omitted] functional calculus and Davies–Gaffney estimates

Let X be a metric space with doubling measure, and L be an operator which has a bounded H ∞ functional calculus and satisfies Davies–Gaffney estimates. In this paper, we develop a theory of Orlicz–Hardy spaces associated to L, including a molecule decomposition, square function characterization and duality of Orlicz–Hardy spaces H L , ω ( X ) . Finally, we show that L has a bounded holomorphic functional calculus in H L , ω ( X ) and the Riesz transform is bounded from H L , ω ( X ) to L ( ω ) .

YopD Self-assembly and Binding to LcrV Facilitate Type III Secretion Activity by Yersinia pseudotuberculosis

YopD-like translocator proteins encoded by several Gram-negative bacteria are important for type III secretion-dependent delivery of anti-host effectors into eukaryotic cells. This probably depends on their ability to form pores in the infected cell plasma membrane, through which effectors may gain access to the cell interior. In addition, Yersinia YopD is a negative regulator essential for the control of effector synthesis and secretion. As a prerequisite for this functional duality, YopD may need to establish molecular interactions with other key T3S components. A putative coiled-coil domain and an alpha-helical amphipathic domain, both situated in the YopD C terminus, may represent key protein-protein interaction domains. Therefore, residues within the YopD C terminus were systematically mutagenized. All 68 mutant bacteria were first screened in a variety of assays designed to identify individual residues essential for YopD function, possibly by providing the interaction interface for the docking of other T3S proteins. Mirroring the effect of a full-length yopD gene deletion, five mutant bacteria were defective for both yop regulatory control and effector delivery. Interestingly, all mutations clustered to hydrophobic amino acids of the amphipathic domain. Also situated within this domain, two additional mutants rendered YopD primarily defective in the control of Yop synthesis and secretion. Significantly, protein-protein interaction studies revealed that functionally compromised YopD variants were also defective in self-oligomerization and in the ability to engage another translocator protein, LcrV. Thus, the YopD amphipathic domain facilitates the formation of YopD/YopD and YopD/LcrV interactions, two critical events in the type III secretion process.

Duality and subdifferential for convex functions on complete [formula omitted] metric spaces

Thanks to the recent concept of quasilinearization of Berg and Nikolaev, we have introduced the notion of duality and subdifferential on complete C A T ( 0 ) (Hadamard) spaces. For a Hadamard space X , its dual is a metric space X ∗ which strictly separates non-empty, disjoint, convex closed subsets of X , provided that one of them is compact. If f : X → ( − ∞ , + ∞ ] is a proper, lower semicontinuous, convex function, then the subdifferential ∂ f : X ⇉ X ∗ is defined as a multivalued monotone operator such that, for any y ∈ X there exists some x ∈ X with x y ⃗ ∈ ∂ f ( x ) . When X is a Hilbert space, it is a classical fact that R ( I + ∂ f ) = X . Using a Fenchel conjugacy-like concept, we show that the approximate subdifferential ∂ ϵ f ( x ) is non-empty, for any ϵ > 0 and any x in efficient domain of f . Our results generalize duality and subdifferential of convex functions in Hilbert spaces.

Beyond Desensitization: Physiological Relevance of Arrestin-Dependent Signaling

Heptahelical G protein-coupled receptors are the most diverse and therapeutically important family of receptors in the human genome. Ligand binding activates heterotrimeric G proteins that transmit intracellular signals by regulating effector enzymes or ion channels. G protein signaling is terminated, in large part, by arrestin binding, which uncouples the receptor and G protein and targets the receptor for internalization. It is clear, however, that heptahelical receptor signaling does not end with desensitization. Arrestins bind a host of catalytically active proteins and serve as ligand-regulated scaffolds that recruit protein and lipid kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into the receptor-arrestin complex. Although many of these arrestin-bound effectors serve to modulate G protein signaling, degrading second messengers and regulating endocytosis and trafficking, other signals seem to extend beyond the receptor-arrestin complex to regulate such processes as protein translation and gene transcription. Although these findings have led to a re-envisioning of heptahelical receptor signaling, little is known about the physiological roles of arrestin-dependent signaling. In vivo, the duality of arrestin function makes it difficult to dissociate the consequences of arrestin-dependent desensitization from those that might be ascribed to arrestin-mediated signaling. Nonetheless, recent evidence generated using arrestin knockouts, G protein-uncoupled receptor mutants, and arrestin pathway-selective "biased agonists" is beginning to reveal that arrestin signaling plays important roles in the retina, central nervous system, cardiovascular system, bone remodeling, immune system, and cancer. Understanding the signaling roles of arrestins may foster the development of pathway-selective drugs that exploit these pathways for therapeutic benefit.