Flowers and weeds: cell-type specific pruning in the developing visual thalamus

In the first weeks of vertebrate postnatal life, neural networks in the visual thalamus undergo activity-dependent refinement thought to be important for the development of functional vision. This process involves pruning of synaptic connections between retinal ganglion cells and excitatory thalamic neurons that relay signals on to visual areas of the cortex. A recent report in Neural Development shows that this does not occur in inhibitory neurons, questioning our current understanding of the development of mature neural circuits. See research article: http://www.neuraldevelopment.com/content/8/1/24     

Genomic database resources for Dictyostelium discoideum

Dictyostelium is an attractive model system for the study of mechanisms basic to cellular function or complex multicellular developmental processes. Recent advances in Dictyostelium genomics have generated a wide spectrum of resources. However, much of the current genomic sequence information is still not currently available through GenBank or related databases. Thus, many investigators are unaware that extensive sequence data from Dictyostelium has been compiled, or of its availability and access. Here, we discuss progress in Dictyostelium genomics and gene annotation, and highlight the primary portals for sequence access, manipulation and analysis (http://genome.imb-jena.de/dictyostelium/; http://dictygenome.bcm.tmc.edu/; http://www.sanger. ac.uk/Projects/D_discoideum/; http://www.csm.biol. tsukuba.ac.jp/cDNAproject.html).     

BRENDA: a resource for enzyme data and metabolic information.

BRENDA (BRaunschweig ENzyme DAtabase), founded in 1987 by Dietmar Schomburg, is a comprehensive protein function database, containing enzymatic and metabolic information extracted from the primary literature. Presently, the database holds data on more than 40 000 enzymes and 4460 different organisms, and includes information about enzyme-ligand relationships with numerous chemical compounds. The collection of molecular and biochemical information in BRENDA provides a fundamental resource for research in biotechnology, pharmacology, medicinal diagnostics, enzyme mechanics, and metabolism. BRENDA is accessible free of charge to the academic community at http://www.brenda.uni-koeln.de/; commercial users need a license available from http://www.science-factory.com/     

Edesign: Primer and Enhanced Internal Probe Design Tool for Quantitative PCR Experiments and Genotyping Assays

Analytical PCR experiments preferably use internal probes for monitoring the amplification reaction and specific detection of the amplicon. Such internal probes have to be designed in close context with the amplification primers, and may require additional considerations for the detection of genetic variations. Here we describe Edesign, a new online and stand-alone tool for designing sets of PCR primers together with an internal probe for conducting quantitative real-time PCR (qPCR) and genotypic experiments. Edesign can be used for selecting standard DNA oligonucleotides like for instance TaqMan probes, but has been further extended with new functions and enhanced design features for Eprobes. Eprobes, with their single thiazole orange-labelled nucleotide, allow for highly sensitive genotypic assays because of their higher DNA binding affinity as compared to standard DNA oligonucleotides. Using new thermodynamic parameters, Edesign considers unique features of Eprobes during primer and probe design for establishing qPCR experiments and genotyping by melting curve analysis. Additional functions in Edesign allow probe design for effective discrimination between wild-type sequences and genetic variations either using standard DNA oligonucleotides or Eprobes. Edesign can be freely accessed online at http://www.dnaform.com/edesign2/, and the source code is available for download.     

Pit-bull reviewing, the pursuit of perfection and the victims of success

Forming synaptic connections of the appropriate strength between specific neurons is crucial for constructing neural circuits to control behavior. A recent paper in Neural Development describes the use of a synapse-specific label in Caenorhabditis elegans to implicate local UNC-6/netrin signaling in this developmental process. Thus, as well as their well known roles in cell migration and axon guidance, UNC-6/netrin signals distinguish an appropriate synaptic partner from other potential targets. See Research article: http://www.neuraldevelopment.com/content/6/1/28     

A motorized microdrive for recording of neural ensembles in awake behaving rats

The recording of neural ensembles in awake, behaving rats has been an extremely successful experimental paradigm, providing demonstrable scientific advances. Dynamic control of the position of the implanted electrodes is of key importance as mobile electrodes provide a better signal-to-noise ratio and a better cell/ electrode yield than nonmobile electrodes. Here we describe the use of low cost, soon to be commercially available dc motors to successfully control the depth of electrodes. The prototype designed is approximately 30 mm in diameter and 50 mm in length and weighed about 30 gms. This paper presents the results of linear displacements of electrodes achievable with this motorized microdrive.     

Design and Assembly of an Ultra-light Motorized Microdrive for Chronic Neural Recordings in Small Animals

The ability to chronically record from populations of neurons in freely behaving animals has proven an invaluable tool for dissecting the function of neural circuits underlying a variety of natural behaviors, including navigation¹ , decision making ^2,3, and the generation of complex motor sequences^4,5,6. Advances in precision machining has allowed for the fabrication of light-weight devices suitable for chronic recordings in small animals, such as mice and songbirds. The ability to adjust the electrode position with small remotely controlled motors has further increased the recording yield in various behavioral contexts by reducing animal handling.^6,7Here we describe a protocol to build an ultra-light motorized microdrive for long-term chronic recordings in small animals. Our design evolved from an earlier published version⁷, and has been adapted for ease-of use and cost-effectiveness to be more practical and accessible to a wide array of researchers. This proven design ^8,9,10,11 allows for fine, remote positioning of electrodes over a range of ~ 5 mm and weighs less than 750 mg when fully assembled. We present the complete protocol for how to build and assemble these drives, including 3D CAD drawings for all custom microdrive components.     

Neural interface with a silicon neural probe in the advancement of microtechnology

In this paper we describe the status of a silicon-based microelectrode for neural recording and an advanced neural interface. We have developed a silicon neural probe, using a combination of plasma and wet etching techniques. This process enables the probe thickness to be controlled precisely. To enhance the CMOS compatibility in the fabrication process, we investigated the feasibility of the site material of the doped polycrystalline silicon with small grains of around 50 nm in size. This silicon electrode demonstrated a favorable performance with respect to impedance spectra, surface topography and acute neural recording. These results showed that the silicon neural probe can be used as an advanced microelectrode for neurological applications.     

Identifying differentially expressed subnetworks with MMG

BACKGROUND: Mixture model on graphs (MMG) is a probabilistic model that integrates network topology with (gene, protein) expression data to predict the regulation state of genes and proteins. It is remarkably robust to missing data, a feature particularly important for its use in quantitative proteomics. A new implementation in C and interfaced with R makes MMG extremely fast and easy to use and to extend. AVAILABILITY: The original implementation (Matlab) is still available from http://www.dcs.shef.ac.uk/~guido/; the new implementation is available from http://wrightlab.group.shef.ac.uk/people_noirel.htm, from CRAN, and has been submitted to BioConductor, http://www.bioconductor.org/.     

A cost-effective protocol for monitoring birds using autonomous recording units: a case study with a night-time singing passerine

Capsule: We describe an effective monitoring protocol for detecting wildlife presence using autonomous recording units (ARUs) under different density scenarios.

Aims: To describe an effective protocol for monitoring a night-time singing passerine, the Dupont’s Lark Chersophilus duponti, using ARUs.

Methods: We estimate, using both simulations and field-collected data, the number of devices needed to reliably detect the species under different density scenarios and to assess recording time and the number of working days needed to ensure species detection. We placed between four and six ARUs in three Dupont’s Lark populations with different bird densities. Devices were programmed to record for 90 minutes per day for four consecutive days. ARUs were deployed between April and June of 2017.

Results: We found large differences in the number of recorders needed to detect species presence under different density scenarios, with more ARUs required in less dense populations. The number of ARUs needed to be differed between estimates obtained by simulations and with field data. This could be related to movements of the monitored species while they were singing. According to our results, the monitoring period for detecting the Dupont’s Lark could be as little as one hour of recording (from one hour before dawn to dawn) and two monitoring days, the minimum monitoring time needed to detect the species in all populations surveyed, regardless of density scenarios.

Conclusion: Our results cannot be directly extrapolated to other singing species since singing behaviour and characteristics greatly differ between species. We describe five logical steps to develop effective wildlife monitoring protocols using ARUs for detecting species presence, which may be helpful for future studies and with different species.     

A novel deconvolution method for modeling UDP-N-acetyl-D-glucosamine biosynthetic pathways based on 13C mass isotopologue profiles under non-steady-state conditions

This article is a response to Wang and Luo. See correspondence article http://www.biomedcentral.com/1741-7007/10/30/ [WEBCITE] and the original research article http://www.biomedcentral.com/1741-7007/9/24 [WEBCITE].     

The Physiome Model Repository 2

MOTIVATION: The Physiome Model Repository 2 (PMR2) software was created as part of the IUPS Physiome Project (Hunter and Borg, 2003), and today it serves as the foundation for the CellML model repository. Key advantages brought to the end user by PMR2 include: facilities for model exchange, enhanced collaboration and a detailed change history for each model. AVAILABILITY: PMR2 is available under an open source license at http://www.cellml.org/tools/pmr/; a fully functional instance of this software can be accessed at http://models.physiomeproject.org/.     

matchprobes: a Bioconductor package for the sequence-matching of microarray probe elements

SUMMARY: The nucleotide sequences of the probes on a microarray can be used for a variety of purposes in the analysis of microarray experiments. We describe software and a paradigm for the creation of data packages for curating, distributing and working with probe sequence data in a uniform, across-types-of-microarrays manner. While the implementation is specific to the Bioconductor project, the ideas and general strategies are more general and could be easily adopted by other projects. AVAILABILITY: The R package matchprobes is available under LGPL at http://www.bioconductor.org SUPPLEMENTARY INFORMATION: The package contains documentation in the form of a vignette and manual pages.     

Database model and specification of GermOnline Release 2.0, a cross-species community annotation knowledgebase on germ cell differentiation

GermOnline is a web-accessible relational database that enables life scientists to make a significant and sustained contribution to the annotation of genes relevant for the fields of mitosis, meiosis, germ line development and gametogenesis across species. This novel approach to genome annotation includes a platform for knowledge submission and curation as well as microarray data storage and visualization hosted by a global network of servers. AVAILABILITY: The database is accessible at http://www.germonline.org/. For convenient world-wide access we have set up a network of servers in Europe (http://germonline.unibas.ch/; http://germonline.igh.cnrs.fr/), Japan (http://germonline.biochem.s.u-tokyo.ac.jp/) and USA (http://germonline.yeastgenome.org/). SUPPLEMENTARY INFORMATION: Extended documentation of the database is available through the link 'About GermOnline' at the websites.     

The Database of Ribosomal Cross-links: an update.

The Database of Ribosomal Cross-links (DRC) was created in 1997. Here we describe new data incorporated into this database and several new features of the DRC. The DRC is freely available via World Wide Web at http://visitweb.com/database/ or http://www. mpimg-berlin-dahlem.mpg.de/ approximately ag_ribo/ag_brimacombe/drc/     

Optogenetic investigation of neural circuits in vivo

The recent development of light-activated optogenetic probes allows for the identification and manipulation of specific neural populations and their connections in awake animals with unprecedented spatial and temporal precision. This review describes the use of optogenetic tools to investigate neurons and neural circuits in vivo. We describe the current panel of optogenetic probes, methods of targeting these probes to specific cell types in the nervous system, and strategies of photostimulating cells in awake, behaving animals. Finally, we survey the application of optogenetic tools to studying functional neuroanatomy, behavior and the etiology and treatment of various neurological disorders.     

Protein kinase C-α negatively regulates EGF-induced PLC- activity through direct phosphorylation

Phospholipase C- is a PLC isozyme that contains a CDC25 homology domain and a pair of RA domains in addition to a conserved PLC catalytic domain. PLC- is activated by both growth factors and GPCR ligands in a distinct manner. Growth factors such as EGF stimulate PLC- in an RA2 domain-dependent manner through Ras and Rap. On the other hand, several GPCR ligands that are linked with Ga₁₂ or Ga₁₃ can activate PLC- by associating with GTP-RhoA. GTP-RhoA binds with the region in the PLC- Y domain. Gs-linked ligands such as PGE1 and adrenaline stimulate PLC- by cAMP-dependent activation of Epac and Rap2B. PLC- is important for cardiac development and function. In addition, several lines of evidence indicate that PLC- promotes cell growth in an activity-dependent or -independent manner. In particular, PLC--dependent suppression of EGF receptor downregulation contributes to its growth promoting activity. Proper regulation of PLC- activity is essential for preventing tumor formation. Our previous report indicated that EGF-dependent ubiquitination of PLC- is required for the control of PLC--dependent cell growth. Recently, we found that PLC- is phosphorylated by growth factor stimulation, and this is another mechanism of the negative regulation. PLC- is phosphorylated by PKC-α upon stimulation with growth factors such as EGF and PDGF. The EGF-induced phosphorylation of PLC- was abolished by PKC inhibitors and by the expression of the dominant negative mutant of PKC-α. Furthermore, PKC-α was found to phosphorylate PLC- directly in vitro, suggesting that PLC- is a substrate of PKC-α in cells. In addition, PLC- was co-immunoprecipitated with PKC-α in an EGF-dependent manner. Immunocytochemical studies showed that PLC- co-localized with PKC-α in the plasma membrane after EGF stimulation. In addition, inhibition of PKC activity enhanced PLC--mediated PIP₂ hydrolysis, suggesting that PKC-α negatively regulates PLC- activity. Taken together, these results suggest for the first time that PLC- is regulated by PKC-α-dependent phosphorylation.