Immunohistochemical expression of Fibrillin-1 in idiopathic epiretinal membranes.

Purpose: To investigate the expression patterns of Fibrillin-1 in idiopathic epiretinal membranes (iERM) and identify Fibrillin-1-secreting cells.

Methods: iERM samples were collected via standard 27-gauge vitrectomy and subsequently subjected to flat-mount immunohistochemistry with double staining for the following markers: Fibrillin-1, glial acidic fibrillary protein (GFAP), cellular retinaldehyde-binding protein (CRALBP), retinoid isomerohydrolase RPE65 (RPE65), and α-smooth muscle actin (α-SMA).

Results: Fibrillin-1 was detected throughout the iERM.

A highly quality genome sequence of Penicillium oxalicum species isolated from the root of Ixora chinensis in Vietnam.

Penicillium oxalicum has been reported as a multienzyme-producing fungus and is widely used in industry due to great potential for cellulase release. Until now, there are only 10 available genome assemblies of P. oxalicum species deposited in the GenBank database.

The familial dementia gene revisited: a missense mutation revealed by whole-exome sequencing identifies ITM2B as a candidate gene underlying a novel autosomal dominant retinal dystrophy in a large family.

Inherited retinal diseases are a group of clinically and genetically heterogeneous disorders for which a significant number of cases remain genetically unresolved. Increasing knowledge on underlying pathogenic mechanisms with precise phenotype-genotype correlation is, however, critical for establishing novel therapeutic interventions for these yet incurable neurodegenerative conditions. We report phenotypic and genetic characterization of a large family presenting an unusual autosomal dominant retinal dystrophy.

Vision and air flow combine to streamline flying honeybees.

Insects face the challenge of integrating multi-sensory information to control their flight. Here we study a 'streamlining' response in honeybees, whereby honeybees raise their abdomen to reduce drag. We find that this response, which was recently reported to be mediated by optic flow, is also strongly modulated by the presence of air flow simulating a head wind.

Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness.

Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder. Two forms can be distinguished clinically: complete CSNB (cCSNB) and incomplete CSNB. Individuals with cCSNB have visual impairment under low-light conditions and show a characteristic electroretinogram (ERG).

Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness.

Congenital stationary night blindness (CSNB) is a heterogeneous retinal disorder characterized by visual impairment under low light conditions. This disorder is due to a signal transmission defect from rod photoreceptors to adjacent bipolar cells in the retina. Two forms can be distinguished clinically, complete CSNB (cCSNB) or incomplete CSNB; the two forms are distinguished on the basis of the affected signaling pathway.

New features that improve the pharmacophore tools from Accelrys.

Generating a pharmacophore is often the first step towards understanding the interactions between a receptor and a ligand and can be pivotal to a successful drug discovery project. The pharmacophore tools at Accelrys have been used to assist in many different projects over the years, such as lead generation, scaffold hopping, mining ligand databases as well as many more. In this article, we will review the pharmacophore tools that have been developed at Accelrys.

Honeybee flight: a novel 'streamlining' response.

Animals that move rapidly through the air can save considerable energy by reducing the drag that they need to overcome during flight. We describe a novel 'streamlining' response in tethered, flying honeybees in which the abdomen is held in a raised position when the visual system is exposed to a pattern of image motion that is characteristic of forward flight. This visually evoked response, which can be elicited without exposing the insect to any airflow, presumably serves to reduce the aerodynamic drag that would otherwise be produced by the abdomen during real flight.

Pharmacophore modeling methods in focused library selection - applications in the context of a new classification scheme.

A pharmacophore is a model which represents the key physico-chemical interactions that mediate biological activity. There is a long history of using pharmacophore modeling methods to select subsets of compounds, focused towards a specific target of interest. This paper will review existing computational methods for deriving and comparing pharmacophore models.

Functional asymmetry of the conserved cystine loops in alphabetagamma GABA A receptors revealed by the response to GABA activation and drug potentiation.

Ligand-gated ion channels respond to specific neurotransmitters by transiently opening an integral membrane ion-selective pore, allowing ions to move down their electrochemical gradient. A distinguishing feature of all members of the ligand-gated ion channel superfamily is the presence of a 13-amino acid disulfide loop (Cys-loop) in the extracellular ligand-binding domain. Structural data derived from the acetylcholine receptor place this loop at the interface between the ligand-binding domain and the transmembrane pore-forming domain where it is ideally located to participate in coupling ligand binding to channel opening.

GABA increases both the conductance and mean open time of recombinant GABAA channels co-expressed with GABARAP.

The single channel properties of recombinant gamma-aminobutyric acid type A (GABA(A))alphabetagamma receptors co-expressed with the trafficking protein GABARAP were investigated using membrane patches in the outside-out patch clamp configuration from transiently transfected L929 cells. In control cells expressing alphabetagamma receptors alone, GABA activated single channels whose main conductance was 30 picosiemens (pS) with a subconductance state of 20 pS, and increasing the GABA concentration did not alter their conductance. In contrast, when GABA(A) receptors were co-expressed with GABARAP, the GABA-activated single channels displayed multiple, high conductances (> or =40 pS), and GABA (> or =10 microM) was able to increase their conductance, up to a maximum of 60 pS.

Combining structure-based drug design and pharmacophores.

Development towards integrated computer-aided drug design methodologies is presented by utilising crystal structure complexes to produce structure-based pharmacophores. These novel pharmacophores represent the ligand features that are involved in interactions with the target protein, as well as the space around the ligand occupied by the protein. The protein-ligand complexes can also yield information about all interactions that ligands could potentially form with the binding site, as well as about the size of the binding cavity.

Conductance of recombinant GABA (A) channels is increased in cells co-expressing GABA(A) receptor-associated protein.

High conductance gamma-aminobutyric acid type A (GABA(A)) channels (>40 picosiemens (pS)) have been reported in some studies on GABA(A) channels in situ but not in others, whereas recombinant GABA(A) channels do not appear to display conductances above 40 pS. Furthermore, the conductance of some native GABA(A) channels can be increased by diazepam or pentobarbital, which are effects not reported for expressed GABA(A) channels. GABARAP, a protein associated with native GABA(A) channels, has been reported to cause clustering of GABA(A) receptors and changes in channel kinetics.