Rearrangement of Retinogeniculate Projection Patterns after Eye-Specific Segregation in Mice

It has been of interest whether and when the rearrangement of neuronal circuits can be induced after projection patterns are formed during development. Earlier studies using cats reported that the rearrangement of retinogeniculate projections could be induced even after eye-specific segregation has occurred, but detailed and quantitative characterization of this rearrangement has been lacking. Here we delineate the structural changes of retinogeniculate projections in the C57BL/6 mouse in response to monocular enucleation (ME) after eye-specific segregation. When ME was performed after eye-specific segregation, rearrangement of retinogeniculate axons in the dorsal lateral geniculate nucleus (dLGN) was observed within 5 days. Although this rearrangement was observed both along the dorsomedial-ventrolateral and outer-inner axes in the dLGN, it occurred more rapidly along the outer-inner axis. We also examined the critical period for this rearrangement and found that the rearrangement became almost absent by the beginning of the critical period for ocular dominance plasticity in the primary visual cortex. Taken together, our findings serve as a framework for the assessment of phenotypes of genetically altered mouse strains as well as provide insights into the mechanisms underlying the rearrangement of retinogeniculate projections

An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA)-expressing tumors

PurposeProstate stem cell antigen (PSCA), a cell surface glycoprotein expressed in normal human prostate and bladder, is over-expressed in the majority of localized prostate cancer and most bone metastases. We have previously shown that the hu1G8 minibody, a humanized anti-PSCA antibody fragment (single-chain Fv-C(H)3 dimer, 80 kDa), can localize specifically and image PSCA-expressing xenografts at 21 h post-injection. However, the humanization and antibody fragment reformatting decreased its apparent affinity. Here, we sought to evaluate PET imaging contrast with affinity matured minibodies.MethodsYeast scFv display, involving four rounds of selection, was used to generate the three affinity matured antibody fragments (A2, A11, and C5) that were reformatted into minibodies. These three affinity matured anti-PSCA minibodies were characterized in vitro, and following radiolabeling with (124)I were evaluated in vivo for microPET imaging of PSCA-expressing tumors.ResultsThe A2, A11, and C5 minibody variants all demonstrated improved affinity compared to the parental (P) minibody and were ranked as follows: A2 > A11 > C5 > P. The (124)I-labeled A11 minibody demonstrated higher immunoreactivity than the parental minibody and also achieved the best microPET imaging contrast in two xenograft models, LAPC-9 (prostate cancer) and Capan-1 (pancreatic cancer), when evaluated in vivo.ConclusionOf the affinity variant minibodies tested, the A11 minibody that ranked second in affinity was selected as the best immunoPET tracer to image PSCA-expressing xenografts. This candidate is currently under development for evaluation in a pilot clinical imaging study

Effects of plasma turbulence on the nonlinear evolution of magnetic island in tokamak

Magnetic islands (MIs), resulting from a magnetic field reconnection, are ubiquitous structures in magnetized plasmas. In tokamak plasmas, recent researches suggested that the interaction between an MI and ambient turbulence can be important for the nonlinear MI evolution, but a lack of detailed experimental observations and analyses has prevented further understanding. Here, we provide comprehensive observations such as turbulence spreading into an MI and turbulence enhancement at the reconnection site, elucidating intricate effects of plasma turbulence on the nonlinear MI evolution

Thienoisoindigo-Based Semiconductor Nanowires Assembled with 2-Bromobenzaldehyde via Both Halogen and Chalcogen Bonding

We fabricated nanowires of a conjugated oligomer and applied them to organic field-effect transistors (OFETs). The supramolecular assemblies of a thienoisoindigo-based small molecular organic semiconductor (TIIG-Bz) were prepared by co-precipitation with 2-bromobenzaldehyde (2-BBA) via a combination of halogen bonding (XB) between the bromide in 2-BBA and electron-donor groups in TIIG-Bz, and chalcogen bonding (CB) between the aldehyde in 2-BBA and sulfur in TIIG-Bz. It was found that 2-BBA could be incorporated into the conjugated planes of TIIG-Bz via XB and CB pairs, thereby increasing the pi - pi stacking area between the conjugated planes. As a result, the driving force for one-dimensional growth of the supramolecular assemblies via pi - pi stacking was significantly enhanced. TIIG-Bz/2-BBA nanowires were used to fabricate OFETs, showing significantly enhanced charge transfer mobility compared to OFETs based on pure TIIG-Bz thin films and nanowires, which demonstrates the benefit of nanowire fabrication using 2-BB

Burst-Time-Dependent Plasticity Robustly Guides ON/OFF Segregation in the Lateral Geniculate Nucleus

Spontaneous retinal activity (known as “waves”) remodels synaptic connectivity to the lateral geniculate nucleus (LGN) during development. Analysis of retinal waves recorded with multielectrode arrays in mouse suggested that a cue for the segregation of functionally distinct (ON and OFF) retinal ganglion cells (RGCs) in the LGN may be a desynchronization in their firing, where ON cells precede OFF cells by one second. Using the recorded retinal waves as input, with two different modeling approaches we explore timing-based plasticity rules for the evolution of synaptic weights to identify key features underlying ON/OFF segregation. First, we analytically derive a linear model for the evolution of ON and OFF weights, to understand how synaptic plasticity rules extract input firing properties to guide segregation. Second, we simulate postsynaptic activity with a nonlinear integrate-and-fire model to compare findings with the linear model. We find that spike-time-dependent plasticity, which modifies synaptic weights based on millisecond-long timing and order of pre- and postsynaptic spikes, fails to segregate ON and OFF retinal inputs in the absence of normalization. Implementing homeostatic mechanisms results in segregation, but only with carefully-tuned parameters. Furthermore, extending spike integration timescales to match the second-long input correlation timescales always leads to ON segregation because ON cells fire before OFF cells. We show that burst-time-dependent plasticity can robustly guide ON/OFF segregation in the LGN without normalization, by integrating pre- and postsynaptic bursts irrespective of their firing order and over second-long timescales. We predict that an LGN neuron will become ON- or OFF-responsive based on a local competition of the firing patterns of neighboring RGCs connecting to it. Finally, we demonstrate consistency with ON/OFF segregation in ferret, despite differences in the firing properties of retinal waves. Our model suggests that diverse input statistics of retinal waves can be robustly interpreted by a burst-based rule, which underlies retinogeniculate plasticity across different species

An overview of biotechnology in Korea

During the 1980s and 1990s, Korea has invested heavily in biotechnology research and development, with the aim of becoming a leading nation in this field. It is important to understand the historical progress of this development in order to appreciate the current state of biotechology in Korea. However, it is equally important to know what research is currently being planned and carried out, and by whom.X111sciescopu

Shining a light on peptide-lipid interactions. Fluorescence methods in the study of membrane-active peptides

The function of several bioactive peptides is mediated by their interaction with cellular membranes. Notwithstanding the great applicative interest in these systems, their mechanism of action is still poorly understood, mainly due to the lack of unambiguous 3D-structural data. Here, we briefly review the structural and functional information available from fluorescence spectroscopic methods to illustrate the prominent role of these techniques in the study of peptide-lipid interactions

The Alignment of Liquid Crystals on the Film Surfaces of Soluble Aromatic Polyimides Bearing t-Butylphenyl and Trimethylsilylphenyl Side Groups

With the study goal of firstly elucidating the anisotropic interactions between oriented polymer chain segments and liquid crystal (LC) molecules, and secondly of determining the contributions of the chemical components of the polymer segments to the film surface topography, LC alignment, pretilt, and anchoring energy, we synthesized three dianhydrides, 1,4-bis(4'-t-butylphenyl)pyromellitic dianhydride (BBPD), 1,4-bis(4'-trimethylsilylphenyl)pyromellitic dianhydride (BTPD), and 2,2'-bis(4 ''-tert-butylphenyl)-4,4',5,5'-biphenyltetracarboxylic dianhydride (BBBPAn), and a series of their organosoluble polyimides, BBPD-ODA, BBPD-NMA, BBPD-MDA, BTPD-FDA, and BBBPAn-FDA, which contain the diamines 4,4'-oxydianiline (ODA), 4,4'-methylenediamine (MDA), and 4,4'-(hexafluoroisopropylidene)dianiline (FDA). All the polyimides were determined to be positive birefringent polymers, regardless of the chemical components. Although all the rubbed polyimide films exhibited microgrooves which were created by rubbing process, the film surface topography varied depending on the polyimides. In all the rubbed films, the polymer chains were unidirectionally oriented along the rubbing direction. However, the degree of in-plane birefringence in the rubbed film varied depending on the polyimides. The rubbing-aligned polymer chains in the polyimide films effectively induced the alignment of nematic LCs along their orientation directors by anisotropic interactions between the preferentially oriented polymer chain segments and the LCs. The azimuthal and polar anchoring energies of the LCs ranged from 0.45x10(-4) - 1.37x10(-4) J/m(2) and from 0.86x10(-5) - 4.26x10(-5) J/m(2), respectively, depending on the polyimides. The pretilt angles of the LCs were in the range 0.10-0.62 degrees. In summary, the soluble aromatic polyimides, reported here are promising LC alignment layer candidates for the production of advanced LC display devices.X116sciescopuskc