Fluctuating ecological networks: A synthesis of maximum-entropy approaches for pattern detection and process inference

1. Ecological networks such as plant–pollinator systems and food webs vary in space and time. This variability includes fluctuations in global properties such as the total number and intensity of interactions in the network but also in the number and intensity of local (i.e. node level) species interactions. 2. Fluctuations of species' properties can significantly affect higher-order network features, for example, robustness and nestedness, and should therefore be taken into account in null models for pattern detection and hypothesis testing. 3. In ecological research, classical null models treat node-level properties as ‘hard’ constraints that cannot fluctuate. Here, we review and synthesize a set of maximum-entropy methods that allow for fluctuating (‘soft’) constraints, offering a new addition to the classical toolkit of the ecologist. We illustrate the methods with some practical examples, pointing to currently available open-source computer codes. We clarify how this approach can be used by experimental ecologists to detect non-random patterns with null models that not only rewire, but also redistribute interaction strengths by allowing fluctuations in the enforced constraints. 4. Explicit modelling of interspecific heterogeneity through local (i.e. species level) fluctuations of topological and quantitative constraints offers a statistically robust and expanded (e.g. including weighted links) set of tools to understand the assembly and resilience of ecological networks

Aerial release of sterile flies using radio-controlled aircraft.

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Functional maturation of isolated neural progenitor cells from the adult rat hippocampus

Although neural progenitor cells (NPCs) may provide a source of new neurons to alleviate neural trauma, little is known about their electrical properties as they differentiate. We have previously shown that single NPCs from the adult rat hippocampus can be cloned in the presence of heparan sulphate chains purified from the hippocampus, and that these cells can be pushed into a proliferative phenotype with the mitogen FGF2 [Chipperfield, H., Bedi, K.S., Cool, S.M. & Nurcombe, V. (2002) Int. J. Dev. Biol., 46, 661-670]. In this study, the active and passive electrical properties of both undifferentiated and differentiated adult hippocampal NPCs, from 0 to 12 days in vitro as single-cell preparations, were investigated. Sparsely plated, undifferentiated NPCs had a resting membrane potential of approximate to -90 mV and were electrically inexcitable. In > 70%, ATP and benzoylbenzoyl-ATP evoked an inward current and membrane depolarization, whereas acetylcholine, noradrenaline, glutamate and GABA had no detectable effect. In Fura-2-loaded undifferentiated NPCs, ATP and benzoylbenzoyl-ATP evoked a transient increase in the intracellular free Ca2+ concentration, which was dependent on extracellular Ca2+ and was inhibited reversibly by pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS), a P2 receptor antagonist. After differentiation, NPC-derived neurons became electrically excitable, expressing voltage-dependent TTX-sensitive Na+ channels, low- and high-voltage-activated Ca2+ channels and delayed-rectifier K+ channels. Differentiated cells also possessed functional glutamate, GABA, glycine and purinergic (P2X) receptors. Appearance of voltage-dependent and ligand-gated ion channels appears to be an important early step in the differentiation of NPCs

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Detrusor overactivity induced by intravesical application of adenosine 5 '-triphosphate under different delivery conditions in rats

Objectives. We investigate the effects of intravesical application of adenosine 5'-triphosphate (ATP) on bladder activity to elucidate the role of urothelial barrier function and ecto-ATPase activity in the ATP-mediated mechanism inducing detrusor overactivity. Methods. Continuous cystometry by an intravesical catheter inserted from the bladder dome was performed in conscious female rats. Results. ATP solutions adjusted to pH 6.0 did not elicit significant detrusor overactivity at a concentration of 60 mM. However, in bladders pretreated with protamine sulfate (10 mg/mL) to increase urothelial permeability, ATP solution (pH 6.0) induced detrusor overactivity by decreasing the intercontraction intervals. These irritant effects of ATIP after protamine treatment were antagonized by P2X receptor antagonists, such as pyridoxal-5-phosphate-6-azophenyl-2',4-disulfonic acid (70 mu mol/kg) and 2',3'-O-(2,4,6, trinitrophenyl) ATP (30 mu mol/kg). These were also suppressed in rats pretreated with systemic capsaicin (125 mg/kg subcutaneously). Alpha,beta-methylene ATP (5 mM, pH 6.0) or ATP (60 mM, pH6) after intravesical infusion of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (5 mM, pH 6.0), an ecto-ATPase inhibitor, induced detrusor overactivity without protamine pretreatment, but the reduction in intercontraction intervals was smaller compared with that with ATP after protamine treatment. Conclusions. Low permeability of bladder epithelium and ecto-ATPase activity can prevent ATP activation of subepithelial P2X receptors to induce bladder overactivity. Thus, enhanced penetration of endogenous ATIP owing to urothelial damage may contribute to urinary frequency and bladder pain in hypersensitive bladder disorders such as interstitial cystitis.</p

Activation kinetics of single P2X receptors

After the primary structure of P2X receptors had been identified, their function had to be characterized on the molecular level. Since these ligand-gated ion channels become activated very quickly after binding of ATP, methods with adequate time resolution have to be applied to investigate the early events induced by the agonist. Single-channel recordings were performed to describe conformational changes on P2X2, P2X4, and P2X7 receptors induced by ATP and also by allosteric receptor modifiers. The main results of these studies and the models of P2X receptor kinetics derived from these observations are reviewed here. The investigation of purinoceptors by means of the patch clamp technique following site-directed mutagenesis will probably reveal more details of P2X receptor function at the molecular level

Antiretroviral (ARV) Therapy in Resource Poor Countries: What do we Need in Real Life?

Significant progresses have been made in the last 5 years towards the ultimate goal to provide universal access to care for all HIV/AIDS patients needing antiretroviral treatment in resource-poor countries. However, many barriers are still to be overcome, including (●) cost of care for the individual, (●) stigma, (●) lack of qualified human resources and infrastructure, especially in the rural setting, (●) rescue drugs for failing patients and (●) pediatric formulations. Priority actions to be promoted if the fight against HIV/AIDS is to be successful include: (i) promoting access to care in the rural areas, (ii) strengthening of basic health infrastructures, (iii) waiving of users’ fee to get ARV, (iv) a larger variety of drugs, with particular regard to fixed dose combination third line drugs and pediatric formulations, (v) local quality training and (vi) high quality basic and translational research. While the universal access to HIV care is crucial in developing countries, a strong emphasis on prevention should be maintained along