We suggest a method to construct a homomorphic encryption scheme for approximate arithmetic. It supports an approximate addition and multiplication of encrypted messages, together with a new rescaling procedure for managing the magnitude of plaintext. This procedure truncates a ciphertext into a smaller modulus, which leads to rounding of plaintext. The main idea is to add a noise following significant figures which contain a main message. This noise is originally added to the plaintext for security, but considered to be a part of error occurring during approximate computations that is reduced along with plaintext by rescaling. As a result, our decryption structure outputs an approximate value of plaintext with a predetermined precision.We also propose a new batching technique for a RLWE-based construction. A plaintext polynomial is an element of a cyclotomic ring of characteristic zero and it is mapped to a message vector of complex numbers via complex canonical embedding map, which is an isometric ring homomorphism. This transformation does not blow up the size of errors, therefore enables us to preserve the precision of plaintext after encoding. In our construction, the bit size of ciphertext modulus grows linearly with the depth of the circuit being evaluated due to rescaling procedure, while all the previous works either require an exponentially large size of modulus or expensive computations such as bootstrapping or bit extraction. One important feature of our method is that the precision loss during evaluation is bounded by the depth of a circuit and it exceeds at most one more bit compared to unencrypted approximate arithmetic such as floating-point operations. In addition to the basic approximate circuits, we show that our scheme can be applied to the efficient evaluation of transcendental functions such as multiplicative inverse, exponential function, logistic function and discrete Fourier transform.

Of 17 genes annotated in the Arabidopsis genome database as cinnamyl alcohol dehydrogenase (CAD) homologues, an in silico analysis revealed that 8 genes were misannotated. Of the remaining nine, six were catalytically competent for NADPH-dependent reduction of p-coumaryl, caffeyl, coniferyl, 5-hydroxyconiferyl, and sinapyl aldehydes, whereas three displayed very low activity and only at very high substrate concentrations. Of the nine putative CADs, two (AtCAD5 and AtCAD4) had the highest activity and homology (Ϸ83% similarity) relative to bona fide CADs from other species. AtCAD5 used all five substrates effectively, whereas AtCAD4 (of lower overall catalytic capacity) poorly used sinapyl aldehyde; the corresponding 270-fold decrease in kenz resulted from higher Km and lower kcat values, respectively. No CAD homologue displayed a specific requirement for sinapyl aldehyde, which was in direct contrast with unfounded claims for a so-called sinapyl alcohol dehydrogenase in angiosperms. AtCAD2, 3, as well as AtCAD7 and 8 (highest homology to sinapyl alcohol dehydrogenase) were catalytically less active overall by at least an order of magnitude, due to increased Km and lower kcat values. Accordingly, alternative and͞or bifunctional metabolic roles of these proteins in plant defense cannot be ruled out. Comprehensive analyses of lignified tissues of various Arabidopsis knockout mutants (for AtCAD5, 6, and 9) at different stages of growth͞ development indicated the presence of functionally redundant CAD metabolic networks. Moreover, disruption of AtCAD5 expression had only a small effect on either overall lignin amounts deposited, or on syringyl-guaiacyl compositions, despite being the most catalytically active form in vitro.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer death worldwide. HCC can be cured by radical therapies if early diagnosis is done while the tumor has remained of small size. Unfortunately, diagnosis is commonly late when the tumor has grown and spread. Thus, palliative approaches are usually applied such as transarterial intrahepatic chemoembolization and sorafenib, an anti-angiogenic agent and MAP kinase inhibitor. This latter is the only targeted therapy that has shown significant, although moderate, efficiency in some individuals with advanced HCC. This highlights the need to develop other targeted therapies, and to this goal, to identify more and more pathways as potential targets. The Wnt pathway is a key component of a physiological process involved in embryonic development and tissue homeostasis. Activation of this pathway occurs when a Wnt ligand binds to a Frizzled (FZD) receptor at the cell membrane. Two different Wnt signaling cascades have been identified, called non-canonical and canonical pathways, the latter involving the β-catenin protein. Deregulation of the Wnt pathway is an early event in hepatocarcinogenesis and has been associated with an aggressive HCC phenotype, since it is implicated both in cell survival, proliferation, migration and invasion. Thus, component proteins identified in this pathway are potential candidates of pharmacological intervention. This review focuses on the characteristics and functions of the molecular targets of the Wnt signaling cascade and how they may be manipulated to achieve anti-tumor effects.

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ATP-gated ionotropic receptors (P2X receptors) are distributed widely in the nervous system. For example, a hetero-oligomeric receptor containing both P2X2 and P2X3 subunits is involved in primary afferent sensation. Each subunit has two membrane-spanning domains. We have used disulfide bond formation between engineered cysteines to demonstrate close proximity between the outer ends of the first transmembrane domain of one subunit and the second transmembrane domain of another. After expression in HEK 293 cells of such modified P2X2 or P2X4 subunits, the disulfide bond formation is evident because an ATP-evoked channel opening requires previous reduction with dithiothreitol. In the hetero-oligomeric P2X2/3 receptor the coexpression of doubly substituted subunits with wild-type partners allows us to deduce that the hetero-oligomeric channel contains adjacent P2X3 subunits but does not contain adjacent P2X2 subunits. The results suggest a "head-to-tail" subunit arrangement in the quaternary structure of P2X receptors and show that a trimeric P2X2/3 receptor would have the composition P2X2(P2X3)2.

GRAS proteins belong to a plant-specific transcription factor family. Currently, 33 GRAS members including a putative expressed pseudogene have been identified in the Arabidopsis genome. With a reverse genetic approach, we have constructed a ''phenome-ready unimutant collection'' of the GRAS genes in Arabidopsis thaliana. Of this collection, we focused on loss-of-function mutations in 23 novel GRAS members. Under standard conditions, homozygous mutants have no obvious morphological phenotypes compared with those of wild-type plants. Expression analysis of GRAS genes using quantitative realtime RT-PCR (qRT-PCR), microarray data mining, and promoter::GUS reporter fusions revealed their tissuespecific expression patterns. Our analysis of protein-protein interaction and subcellular localization of individual GRAS members indicated their roles as transcription regulators. In our yeast two-hybrid (Y2H) assay, we confirmed the protein-protein interaction between SHORT-ROOT (SHR) and SCARECROW (SCR). Furthermore, we identified a new SHR-interacting protein, SCARECROW-LIKE23 (SCL23), which is the most closely related to SCR. Our large-scale analysis provides a comprehensive evaluation on the Arabidopsis GRAS members, and also our phenome-ready unimutant collection will be a useful resource to better understand individual GRAS proteins that play diverse roles in plant growth and development.

Background/Aims-The canonical Wnt signaling is frequently activated in human hepatocellular carcinoma (HCC). We previously demonstrated that up-regulation of Frizzled-7 receptor (FZD7) in HCC was associated with nuclear accumulation of wild-type β-catenin. Here, we investigated Wnt ligand(s) that may activate the Wnt/β-catenin pathway through FZD7 in HCC cells. Results-In hepatitis B virus (HBV)-induced HCC, Wnt3 was upregulated in tumor and peritumoral tissues compared to normal liver and downstream β-catenin target genes were also increased in these samples. Activation of the Wnt/β-catenin pathway in FOCUS-Wnt3 cells was demonstrated by β-catenin accumulation, enhanced TCF transcriptional activity and proliferation rate. The activation of Wnt/β-catenin signaling in FOCUS-Wnt3 was abolished by a knockdown of FZD7 expression by siRNA. More important, a specific Wnt3-FZD7 interaction was observed by co-immunoprecipitation experiments, which suggest that the action of Wnt3 was mediated via FZD7. Methods-To identifyConclusions-These findings demonstrate a functional interaction between Wnt3 and FZD7 leading to activation of the Wnt/β-catenin signaling pathway in HCC cells and may play a role during hepatocarcinogenesis.

We constructed a full-length human P2X 5 purinoceptor cDNA by incorporating a sequence corresponding to exon 10, which is missing in cDNAs cloned previously from human tissues. We studied the functional properties by patch-clamp recording and fluorescence imaging after expression in human embryonic kidney 293 cells. ATP (1-100 M; half-maximal current at 4 M) elicited inward currents at Ϫ60 mV; these persisted during brief (2 s) applications but declined during longer applications. The peak current was dependent on the holding potential and showed little rectification; however, both the desensitization during the application and the decline in the current when ATP was washed out were slower at ϩ30 mV than at Ϫ60 mV. 2Ј,3Ј-O-(4-Benzoyl)-benzoyl-ATP and ␣␤-methylene-ATP mimicked the action of ATP (half-maximal concentrations 6 and 161 M, respectively). The currents were inhibited by suramin, pyridoxal-5-phosphate-6-azo-2Ј,4Ј-disulfonic acid and Brilliant Blue G, with half-maximal inhibition at 3, 0.2, and 0.5 M, respectively; 2Ј,3Ј-O-(2Ј,4Ј,6Ј-trinitrophenol)-ATP (1 M) was ineffective. Removing divalent cations did not significantly alter ATP concentration-response curves. Reversal potential measurements showed that the human P2X 5 receptor was permeable to calcium (P Ca /P Na ϭ 1.5) and N-methyl-D-glucamine (NMDG) (P NMDG /P Na ϭ 0.4); it was also permeable to chloride (P Cl /P Na ϭ 0.5) but not gluconate (P gluc /P Na ϭ 0.01) ions. The permeability to NMDG developed as quickly as the channel opened, in contrast to the P2X 7 receptor where the NMDG permeability develops over several seconds. Cells expressing human P2X 5 receptors also rapidly accumulated the propidium dye YO-PRO-1 in response to ATP.A P2X 5 subunit cDNA was first isolated from libraries of rat sympathetic ganglia (Collo et al., 1996) and heart (Garcia-Guzman et al., 1996). The RNA is expressed predominantly in heart (Garcia-Guzman et al., 1996) but there is also expression in brain, spinal cord, and adrenal gland (GarciaGuzman et al., 1996). Immunoreactivity for P2X 5 subunits has also been described in developing skeletal muscle of the rat (Meyer et al., 1999;Ryten et al., 2001); recently, the receptor has been implicated in the differentiation of satellite cells into mature multinucleated muscle fibers (Ryten et al., 2002). Mammalian skin and endocrine (Glass and Burnstock, 2001) cells also show P2X 5 immunoreactivity.When expressed in HEK293 cells, the rat P2X 5 subunit cDNAs gave rise to currents activated by ATP, but these were very small and their properties not extensively studied. The current was elicited by ATP [half-maximal concentration (EC 50 ) about 10 M] but not by ␣␤meATP, and it was readily blocked by suramin and PPADS in the 1 to 10 M concentration range (Collo et al., 1996;Garcia-Guzman et al., 1996). A mouse cDNA has also been cloned and expressed; again, the currents recorded from HEK293 cells were only a few tens of picoamperes and they were not studied in detail . On the other hand, although these two mammalian recep...