Central pattern generators deciphered by molecular genetics

Central pattern generators (CPGs) are localized neuronal networks that have the ability to produce rhythmic movements even in the absence of movement-related sensory feedback. They are found in all animals, including man, and serve as informative model systems for understanding how neuronal networks produce behavior. Traditionally, CPGs have been investigated with electrophysiological techniques. Here we review recent molecular and genetic approaches for dissecting the organization and development of CPGs.     

How Much Sorting Is Enough

One strategy for mitigating the effects of rapidly growing global materials consumption is intensified recycling. A key barrier to recycling is the ability to segment or sort constituents within end‐of‐life products. Various sorting technologies hold promise, but each must demonstrate added value to achieve wide‐scale deployment. Potential factors affecting such value include the mix of scrap supply, the nature and mix of finished goods demand, sorting technology performance, and costs. This article examines the use of optimization models to identify economically efficient sorting strategies and their impact on scrap usage. Using this method, this article attempts to identify the conditions that amplify and mute the value of sorting to facilitate recycling. When this method is applied to a case representative of European aluminum secondary production, it is clear that sorting methods can add value in a broad range of conditions. Although better sorting performance (in the form of segmentation efficiency, referred to as recovery rate) correlates positively with cost savings and scrap utilization, it does not always vary monotonically with optimal sorter utilization (i.e., the fraction of scrap sorted rather than unsorted). Furthermore, the case analysis indicates that the value of sorting is more strongly dependent on recovery rate for the more heterogeneous fraction, which, in the case of aluminum, is the cast‐like fraction. Ultimately, sorting increases production flexibility, making a recycler more economically resilient in the face of changing supply and production conditions.     

Migration potential of the banana weevil Cosmopolites sordidus

• 1 The banana weevil Cosmopolites sordidus Germar (Coleoptera: Curculionidae) is a major pest in banana (Musa spp.) growing areas. The weevil is known to be relatively sedentary and closely associated with its host plant but little is known about the species' ability to migrate between banana fields and in nonhost habitats.
• 2 Mark–recapture experiments were conducted to assess the weevils' migration potential, possible differences between the sexes, and the relative attractiveness of pseudostem and pheromone baits.
• 3 One thousand two hundred marked weevils were released in the nonhost habitat at five distances (5, 10, 20, 40 and 70 m) from fresh pseudostem, and from pitfall traps baited with 45 mg of sordidin.
• 4 Two hundred males and 200 females were marked and released at five distances (5, 10, 20, 40 and 70 m) from the pheromone traps.
• 5 Distance and distance/bait interactions had a significant effect on recaptured weevils (binary logistic regression). The two baits were almost equally attractive to weevils in the range 0–10 m, whereas the pheromone was more attractive in the range 10–100 m.
• 6 Distance, bait and distance/bait interactions had a significant effect on the time elapsed from release to recapture (regression with life data) but the pattern observed was not consistent.
• 7 There was no significant difference between males and females with respect to distance or time elapsed from release to recapture.
• 8 The results obtained in the present study show that the migration potential of the banana weevil is greater than previously reported. This should be taken into account when new banana fields are established with clean planting material.

     

Delayed β-cell response and glucose intolerance in young women with Turner syndrome

Background

Accurately monitoring adherence to treatment with recombinant human growth hormone (r-hGH) enables appropriate intervention in cases of poor adherence. The electronic r-hGH auto-injector, easypod?, automatically records the patient's adherence to treatment. This study evaluated adherence to treatment of children who started using the auto-injector and assessed opinions about the device.

Methods

A multicentre, multinational, observational 3-month survey in which children received r-hGH as part of their normal care. Physicians reviewed the recorded dose history and children (with or without parental assistance) completed a questionnaire-based survey. Children missing ≤2 injections per month (92% of injections given) were considered adherent to treatment. Adherence was compared between GH treatment-naïve and treatment-experienced children.

Results

Of 834 recruited participants, 824 were evaluated. The median (range) age was 11 (1-18) years. From the recorded dose history, 87.5% of children were adherent to treatment over the 3-month period. Recorded adherence was higher in treatment-naïve (89.7%, n = 445/496) than in treatment-experienced children (81.7%, n = 152/186) [Fisher's exact test FI(X) = 7.577; p = 0.0062]. According to self-reported data, 90.2% (607/673) of children were adherent over 3 months; 51.5% (421/817) missed ≥1 injection over this period (mainly due to forgetfulness). Concordance between reported and recorded adherence was 84.3%, with a trend towards self-reported adherence being higher than recorded adherence. Most children liked the auto-injector: over 80% gave the top two responses from five options for ease of use (720/779), speed (684/805) and comfort (716/804). Although 38.5% (300/780) of children reported pain on injection, over half of children (210/363) considered the pain to be less or much less than expected. Given the choice, 91.8% (732/797) of children/parents would continue using the device.

Conclusions

easypod? provides an accurate method of monitoring adherence to treatment with r-hGH. In children who received treatment with r-hGH using easypod?, short-term adherence is good, and significantly higher in treatment-naïve children compared with experienced children. Children/parents rate the device highly. The high level of acceptability of the device is reflected by a desire to continue using it by over 90% of the children in the survey.     

The Host-Pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains

Background

Cyclophilin A (CypA) represents a potential key molecule in future antiretroviral therapy since inhibition of CypA suppresses human immunodeficiency virus type 1 (HIV-1) replication. CypA interacts with the virus proteins Capsid (CA) and Vpr, however, the mechanism through which CypA influences HIV-1 infectivity still remains unclear.

Results

Here the interaction of full-length HIV-1 Vpr with the host cellular factor CypA has been characterized and quantified by surface plasmon resonance spectroscopy. A C-terminal region of Vpr, comprising the 16 residues ⁷⁵GCRHSRIGVTRQRRAR⁹⁰, with high binding affinity for CypA has been identified. This region of Vpr does not contain any proline residues but binds much more strongly to CypA than the previously characterized N-terminal binding domain of Vpr, and is thus the first protein binding domain to CypA described involving no proline residues. The fact that the mutant peptide Vpr^75-90 R80A binds more weakly to CypA than the wild-type peptide confirms that Arg-80 is a key residue in the C-terminal binding domain. The N- and C-terminal binding regions of full-length Vpr bind cooperatively to CypA and have allowed a model of the complex to be created. The dissociation constant of full-length Vpr to CypA was determined to be approximately 320 nM, indicating that the binding may be stronger than that of the well characterized interaction of HIV-1 CA with CypA.

Conclusions

For the first time the interaction of full-length Vpr and CypA has been characterized and quantified. A non-proline-containing 16-residue region of C-terminal Vpr which binds specifically to CypA with similar high affinity as full-length Vpr has been identified. The fact that this is the first non-proline containing binding motif of any protein found to bind to CypA, changes the view on how CypA is able to interact with other proteins. It is interesting to note that several previously reported key functions of HIV-1 Vpr are associated with the identified N- and C-terminal binding domains of the protein to CypA.     

A Laboratory Assessment of Potentials and Limitations of Using EDTA,Rhamnolipids, and Compost-derived Humic Substances (HS) in Enhanced Phytoextraction of Copper and Zinc Polluted Calcareous Soils

Phytoextraction is an economically and environmentally attractive in-situ method for cleaning heavy metal polluted soil. Phytoextraction is a rather slow process, but it can be enhanced by the application of chelating agents such as the synthetic ethylenediaminetetraacetic acid (EDTA). However, EDTA is persistent, toxic, and can promote heavy metal leaching. Replacement of EDTA by natural, non-toxic compounds such as humic substances (HS) or rhamnolipids (bacterial-produced biosurfactants) might be environmentally attractive but before recommending such alternatives, their suitability must be assessed. Therefore, compost-derived HS and rhamnolipids were compared with EDTA as natural non-toxic alternatives in a multi-step batch extraction test. The test included 10 steps carried out on two Cu and Zn polluted calcareous soils using a solution:soil ratio of 10 (L/kg). In each step, soil was extracted with an extractant containing EDTA, HS, or rhamnolipids corresponding to 250 mmol DOC/kg of soil (3 g C/kg). By HS extraction, each step resulted in the release of ～0.29 mg Cu/L and ～0.19 mg Zn/L, which is considered to enhance plant uptake without leading to unacceptable leaching and toxification of the plants (and the environment), suggesting HS can enhance phytoextraction. In contrast, the EDTA and the rhamnolipid treatments were found to be unsuitable because the EDTA released Cu and Zn in concentrations that may be toxic to plants and can lead to leaching, whereas the rhamnolipids showed insufficient capacity to mobilize Cu (and Zn). However, future investigations in the field are needed to confirm these laboratory results.     

Controlling the Morphology and Efficiency of Hybrid ZnO:Polythiophene Solar Cells Via Side Chain Functionalization

The efficiency of polymer – metal oxide hybrid solar cells depends critically on the intimacy of mixing of the two semiconductors. The effect of side chain functionalization on the morphology and performance of conjugated polymer:ZnO solar cells is investigated. Using an ester‐functionalized side chain poly(3‐hexylthiophene‐2,5‐diyl) derivative (P3HT‐E), the nanoscale morphology of ZnO:polymer solar cells is significantly more intimately mixed compared to ZnO:poly(3‐hexylthiophene‐2,5‐diyl) (ZnO:P3HT), as evidenced experimentally from a 3D reconstruction of the phase separation using electron tomography. Photoinduced absorption reveals nearly quantitative charge generation for the ZnO:P3HT‐E blend but not for ZnO:P3HT, consistent with the results obtained from solving the 3D diffusion equation for excitons formed in the polymer within the two experimental ZnO morphologies. For thin ZnO:P3HT‐E active layers (～50 nm) this yields a significant improvement of the solar cell performance. For thicker cells, however, the reduced hole mobility and a reduced percolation of ZnO pathways hinders charge carrier collection, limiting the power conversion efficiency.     

Human leukocyte antigen (HLA) class I restricted epitope discovery in yellow fewer and dengue viruses: importance of HLA binding strength

Epitopes from all available full-length sequences of yellow fever virus (YFV) and dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV epitopes were selected using the EpiSelect algorithm to allow for optimal coverage of viral strains. The selected predicted epitopes were synthesized and approximately 75% were found to bind the predicted restricting HLA molecule with an affinity, K(D), stronger than 500 nM. The immunogenicity of 25 HLA-A*02:01, 28 HLA-A*24:02 and 28 HLA-B*07:02 binding peptides was tested in three HLA-transgenic mice models and led to the identification of 17 HLA-A*02:01, 4 HLA-A*2402 and 4 HLA-B*07:02 immunogenic peptides. The immunogenic peptides bound HLA significantly stronger than the non-immunogenic peptides. All except one of the immunogenic peptides had K(D) below 100 nM and the peptides with K(D) below 5 nM were more likely to be immunogenic. In addition, all the immunogenic peptides that were identified as having a high functional avidity had K(D) below 20 nM. A*02:01 transgenic mice were also inoculated twice with the 17DD YFV vaccine strain. Three of the YFV A*02:01 restricted peptides activated T-cells from the infected mice in vitro. All three peptides that elicited responses had an HLA binding affinity of 2 nM or less. The results indicate the importance of the strength of HLA binding in shaping the immune response.