Noise-induced divisive gain control in neuron models

A recent computational study of gain control via shunting inhibition has shown that the slope of the frequency-versus-input (f-I) characteristic of a neuron can be decreased by increasing the noise associated with the inhibitory input (Neural Comput. 13, 227-248). This novel noise-induced divisive gain control relies on the concommittant increase of the noise variance with the mean of the total inhibitory conductance. Here we investigate this effect using different neuronal models. The effect is shown to occur in the standard leaky integrate-and-fire (LIF) model with additive Gaussian white noise, and in the LIF with multiplicative noise acting on the inhibitory conductance. The noisy scaling of input currents is also shown to occur in the one-dimensional theta-neuron model, which has firing dynamics, as well as a large scale compartmental model of a pyramidal cell in the electrosensory lateral line lobe of a weakly electric fish. In this latter case, both the inhibition and the excitatory input have Poisson statistics; noise-induced divisive inhibition is thus seen in f-I curves for which the noise increases along with the input I. We discuss how the variation of the noise intensity along with inputs is constrained by the physiological context and the class of model used, and further provide a comparison of the divisive effect across models.     

Elg1, an alternative subunit of the RFC clamp loader,preferentially interacts with SUMOylated PCNA

Replication‐factor C (RFC) is a protein complex that loads the processivity clamp PCNA onto DNA. Elg1 is a conserved protein with homology to the largest subunit of RFC, but its function remained enigmatic. Here, we show that yeast Elg1 interacts physically and genetically with PCNA, in a manner that depends on PCNA modification, and exhibits preferential affinity for SUMOylated PCNA. This interaction is mediated by three small ubiquitin‐like modifier (SUMO)‐interacting motifs and a PCNA‐interacting protein box close to the N‐terminus of Elg1. These motifs are important for the ability of Elg1 to maintain genomic stability. SUMOylated PCNA is known to recruit the helicase Srs2, and in the absence of Elg1, Srs2 and SUMOylated PCNA accumulate on chromatin. Strains carrying mutations in both ELG1 and SRS2 exhibit a synthetic fitness defect that depends on PCNA modification. Our results underscore the importance of Elg1, Srs2 and SUMOylated PCNA in the maintenance of genomic stability.     

Glycerol triacetate as solvent and acyl donor in the production of isoamyl acetate with Candida antarctica lipase B

Glycerol triacetate was successfully used as a green solvent and as the acyl donor in the transesterification of isoamyl alcohol to produce isoamyl acetate using free and immobilized Candida antarctica lipase B. Immobilized lipase was more catalytically active than free lipase and could be easily separated from the reaction mixture by filtration. In addition, it was found that increasing either the reaction temperature or the enzyme to substrate ratio increased the conversion of isoamyl alcohol. Using triacetin as the solvent also enabled the separation of product by simple extraction with petroleum ether and catalyst recycling.     

Analysis of membrane protein genes in a Brazilian isolate of Anaplasma marginale

The sequencing of the complete genome of Anaplasma marginale has enabled the identification of several genes that encode membrane proteins, thereby increasing the chances of identifying candidate immunogens. Little is known regarding the genetic variability of genes that encode membrane proteins in A. marginale isolates. The aim of the present study was to determine the degree of conservation of the predicted amino acid sequences of OMP1, OMP4, OMP5, OMP7, OMP8, OMP10, OMP14, OMP15, SODb, OPAG1, OPAG3, VirB3, VirB9-1, PepA, EF-Tu and AM854 proteins in a Brazilian isolate of A. marginale compared to other isolates. Hence, primers were used to amplify these genes: omp1, omp4, omp5, omp7, omp8, omp10, omp14, omp15, sodb, opag1, opag3, virb3, VirB9-1, pepA, ef-tu and am854. After polimerase chain reaction amplification, the products were cloned and sequenced using the Sanger method and the predicted amino acid sequence were multi-aligned using the CLUSTALW and MEGA 4 programs, comparing the predicted sequences between the Brazilian, Saint Maries, Florida and A. marginale centrale isolates. With the exception of outer membrane protein (OMP) 7, all proteins exhibited 92-100% homology to the other A. marginale isolates. However, only OMP1, OMP5, EF-Tu, VirB3, SODb and VirB9-1 were selected as potential immunogens capable of promoting cross-protection between isolates due to the high degree of homology (over 72%) also found with A. (centrale) marginale.     

Adrenomedullin and its receptor components in adipose tissues: Differences between white and brown fats and the effects of adrenergic stimulation

Male Sprague-Dawley rats were subcutaneously injected with 2.5mg/kg phenylephrine or 2.5mg/kg isoproterenol or both (2.5mg/kg for each drug) for 4 days, twice a day. Samples of scapular brown adipose tissue (BAT) and epididymal white adipose tissue (WAT) were collected for the measurement of adrenomedullin (AM) levels and the gene expression of preproAM, calcitonin receptor like receptor (CRLR) and its activity modifying proteins (RAMPs) by radioimmunoassay and RT-PCR. These values were compared with those in the rats that received 0.9% saline. The gene expression of AM and AM receptor components in BAT are much less than that in epididymal WAT. In BAT there were an increase in AM peptide level after a combined treatment of alpha(1) and beta adrenoceptor agonists and increases in preproAM mRNA levels for rats treated with alpha(1) and beta receptor agonists alone or in combination. Both CRLR and RAMP2 mRNA levels of alphabeta group were increased significantly. In WAT, AM peptide level, RAMP1 and RAMP2 mRNA expression levels were augmented in the alpha group while CRLR mRNA level was enhanced in the beta group. The levels of AM, its receptor and RAMPs are much less in BAT than in WAT but adrenergic stimulation has a greater effect on the AM and its receptor components in BAT than those in WAT. AM stimulates lipolysis and increases the level of uncoupling protein-1 (UCP-1) in BAT. It may therefore enhance thermogenesis by increasing the availability of free fatty acids substrate as well as the UCP-1 level on the mitochondrial membrane.     

The nuclear RhoA exchange factor Net1 interacts with proteins of the Dlg family, affects their localization, and influences their tumor suppressor activity

Net1 is a RhoA-specific guanine nucleotide exchange factor which localizes to the nucleus at steady state. A deletion in its N terminus redistributes the protein to the cytosol, where it activates RhoA and can promote transformation. Net1 contains a PDZ-binding motif at the C terminus which is essential for its transformation properties. Here, we found that Net1 interacts through its PDZ-binding motif with tumor suppressor proteins of the Dlg family, including Dlg1/SAP97, SAP102, and PSD95. The interaction between Net1 and its PDZ partners promotes the translocation of the PDZ proteins to nuclear subdomains associated with PML bodies. Interestingly, the oncogenic mutant of Net1 is unable to shuttle the PDZ proteins to the nucleus, although these proteins still associate as clusters in the cytosol. Our results suggest that the ability of oncogenic Net1 to transform cells may be in part related to its ability to sequester tumor suppressor proteins like Dlg1 in the cytosol, thereby interfering with their normal cellular function. In agreement with this, the transformation potential of oncogenic Net1 is reduced when it is coexpressed with Dlg1 or SAP102. Together, our results suggest that the interaction between Net1 and Dlg1 may contribute to the mechanism of Net1-mediated transformation.