Stochasticity,Bistability and the Wisdom of Crowds: A Model for Associative Learning in Genetic Regulatory Networks

It is generally believed that associative memory in the brain depends on multistable synaptic dynamics, which enable the synapses to maintain their value for extended periods of time. However, multistable dynamics are not restricted to synapses. In particular, the dynamics of some genetic regulatory networks are multistable, raising the possibility that even single cells, in the absence of a nervous system, are capable of learning associations. Here we study a standard genetic regulatory network model with bistable elements and stochastic dynamics. We demonstrate that such a genetic regulatory network model is capable of learning multiple, general, overlapping associations. The capacity of the network, defined as the number of associations that can be simultaneously stored and retrieved, is proportional to the square root of the number of bistable elements in the genetic regulatory network. Moreover, we compute the capacity of a clonal population of cells, such as in a colony of bacteria or a tissue, to store associations. We show that even if the cells do not interact, the capacity of the population to store associations substantially exceeds that of a single cell and is proportional to the number of bistable elements. Thus, we show that even single cells are endowed with the computational power to learn associations, a power that is substantially enhanced when these cells form a population.     

Enhanced inhibition of Aspergillus niger on sedge (Lepironia articulata) treated with heat‐cured lime oil

Aims

This study aimed to examine heat curing effect (30–100°C) on antifungal activities of lime oil and its components (limonene, p‐cymene, β‐pinene and α‐pinene) at concentrations ranging from 100 to 300 μl ml^?1 against Aspergillus niger in microbiological medium and to optimize heat curing of lime oil for efficient mould control on sedge (Lepironia articulata).

Methods and Results

Broth dilution method was employed to determine lime oil minimum inhibitory concentration, which was at 90 μl ml^?1 with heat curing at 70°C. Limonene, a main component of lime oil, was an agent responsible for temperature dependencies of lime oil activities observed. Response surface methodology was used to construct the mathematical model describing a time period of zero mould growth on sedge as functions of heat curing temperature and lime oil concentration. Heat curing of 90 μl ml^?1 lime oil at 70°C extended a period of zero mould growth on sedge to 18 weeks under moist conditions.

Conclusions

Heat curing at 70°C best enhanced antifungal activity of lime oil against A. niger both in medium and on sedge.

Significance and Impact of the Study

Heat curing of lime oil has potential to be used to enhance the antifungal safety of sedge products.     

The Sodium Storage Mechanism in Tunnel‐Type Na0.44MnO2 Cathodes and the Way to Ensure Their Durable Operation

Tunnel‐type sodium manganese oxide is a promising cathode material for aqueous/nonaqueous sodium‐ion batteries, however its storage mechanism is not fully understood, in part due to the complicated sodium intercalation process. In addition, low cyclability due to manganese dissolution has limited its practical application in rechargeable batteries. Here, the intricate sodium intercalation mechanism of Na_0.44MnO₂ is revealed by combination of electrochemical characterization, structure determination from powder X‐ray diffraction data, 3D bond valence difference maps, and barrier‐energy calculations of the sodium diffusion. NaI is proposed as an important electrolyte solution additive. It is shown to form a thin, beneficial, and durable cathode surface film that prevents manganese dissolution. The addition of 0.01 m NaI to electrolyte solutions based on alkyl carbonate solvents and NaClO₄ greatly improves the cycling efficiency, raising the capacity retention from 86% to 96% after 600 cycles. This study determines the core aspects of the sodium intercalation mechanism in tunnel‐type sodium manganese oxide and shows how it can serve as a durable cathode material for rechargeable Na batteries.     

Repeated,Long-Term Cycling of Putative Stem Cells between Niches in a Basal Chordate

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Highlights? Identification of a niche for germline and somatic stem cells in a basal chordate ? Stem cells repeatedly migrate between aged or damaged niches into developing niches     

Surface properties and reduced biofouling of graft-copolymers that possess oppositely charged groups

Microbial biofilms and their components present a major obstacle for ensuring the long-term effectiveness of membrane processes. Graft polymerization on membrane surfaces, in general, and grafting with oppositely charged monomers, have been shown to reduce biofouling significantly. In this study, surface forces and macromolecular properties of graft copolymers that possess oppositely charged groups were related to their potent antibiofouling behavior. Graft polymerization was performed using the negatively charged 3-sulphopropyl methacrylate (SPM) and positively charged [2-(methacryloyloxy)ethyl]-trimethylammonium (MOETMA) monomers to yield a copolymer layer on polyvinylidene fluoride (PVDF) surface. Quartz crystal microbalance with dissipation monitoring (QCM-D) technology was used to monitor the reduced adsorption of extracellular polymeric substances (EPS) extracted from a membrane bioreactor (MBR) wastewater treatment facility. Complemented measurements of attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy provided evaluation of the antifouling properties of the surface. Increase in water content in grafted layer exposed to 100 mM aqueous NaCl solution was observed by QCM-D. Therefore, the grafted copolymer layer is swelled in the presence of 100 mM NaCl because of reversing of polymer self-association by counterions. Force measurements by atomic force microscopy (AFM) showed an increased repulsion between a carboxylate-modified latex (CML) particle probe and a modified PVDF surface, especially in the presence of 100 mM NaCl. The hydration and swelling of the grafted polymer layer are shown to repel EPS and reduce their adsorption. Delineating the surface properties of antifouling grafted layers may lead to the design of novel antifouling surfaces.     

Co-evolving residues in membrane proteins

MOTIVATION: The analysis of co-evolving residues has been exhaustively evaluated for the prediction of intramolecular amino acid contacts in soluble proteins. Although a variety of different methods for the detection of these co-evolving residues have been developed, the fraction of correctly predicted contacts remained insufficient for their reliable application in the construction of structural models. Membrane proteins, which constitute between one-fourth and one-third of all proteins in an organism, were only considered in few individual case studies. RESULTS: We present the first general study of correlated mutations in alpha-helical membrane proteins. Using seven different prediction algorithms, we extracted co-evolving residues for 14 membrane proteins having a solved 3D structure. On average, distances between correlated pairs of residues lying on different transmembrane segments were found to be significantly smaller compared to a random prediction. Covariation of residues was frequently found in direct sequence neighborhood to helix-helix contacts. Based on the results obtained from individual prediction methods, we constructed a consensus prediction for every protein in the dataset that combines obtained correlations from different prediction algorithms and simultaneously removes likely false positives. Using this consensus prediction, 53% of all predicted residue pairs were found within one helix turn of an observed helix-helix contact. Based on the combination of co-evolving residues detected with the four best prediction algorithms, interacting helices could be predicted with a specificity of 83% and sensitivity of 42%. AVAILABILITY: http://webclu.bio.wzw.tum.de/helixcorr/     

Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural analogues as TNF-alpha and IL-6 inhibitors

In the present article, we have synthesized three different series of pyrazolo[3,4-b]pyridines and their structural analogues using novel synthetic strategy involving one-pot condensation of 5,6-dihydro-4H-pyran-3-carbaldehyde/2-formyl-3,4,6-tri-O-methyl-D-glucal/chromone-3-carbaldehyde with heteroaromatic amines. All synthesized compounds were evaluated for their anti-inflammatory activity against TNF-alpha and IL-6. Out of 28 compounds screened, 40, 51, 52 and 56 exhibited promising activity against IL-6 with 60-65% inhibition at 10 microM concentration. Amongst these, 51, 52 and 56 showed potent IL-6 inhibitory activity with IC(50)'s of 0.2, 0.3 and 0.16 microM, respectively. Compound 56 was not cytotoxic in CCK-8 cells up to the concentration of >100 microM.     

Bacterial and eukaryote microbiomes of mosquito habitats in dengue-endemic southern Taiwan

Mosquitoes interact with the microbiome of the waters where they oviposit in several ways. Past work suggests adult mosquitoes can detect certain microbes that stimulate oviposition. The presence or absence of certain microbes in water containers thus can attract or repel mosquito species to different containers. I hypothesized that these relationships could be detected via metagenomics. I focused on two container breeders that coexist in Southern Taiwan: the dengue vector Aedes aegypti and the less competent vector Ae. albopictus. In addition to culturing, I performed 16S and 18S rDNA metagenomics assays, the latter of which had never been applied to mosquito waters before, to identify the microbial diversity of artificial containers with and without mosquito larvae. I found no correlation between mosquito presence to any features of the containers or to their microbiomes, which instead correlated strongly with location. Microbial diversity across containers was highly variable, even within the same location, with multiple taxa only found in single containers. This variability is reasonable, because mosquito gut microbiomes are also extremely variable. The possibility remains that microbes in natural containers differ significantly from those in artificial containers, and that these differences drive Aedes preferences for human-associated containers. Broad, single-microbe experimental work is recommended to identify possible attractant or repellent microbial taxa.     

Tyrosine phosphorylation of WW proteins

A number of key regulatory proteins contain one or two copies of the WW domain known to mediate protein–protein interaction via proline-rich motifs, such as PPxY. The Hippo pathway components take advantage of this module to transduce tumor suppressor signaling. It is becoming evident that tyrosine phosphorylation is a critical regulator of the WW proteins. Here, we review the current knowledge on the involved tyrosine kinases and their roles in regulating the WW proteins.