Hidden magnetic transitions in thermoelectric layered cobaltite, [Ca2_2CoO3_3]0.62_{0.62}[CoO2_2]

A positive muon spin rotation and relaxation ($\mu^+$SR) experiment on [Ca$_2$CoO$_3$]$_{0.62}$[CoO$_2$], ({\sl i.e.}, Ca$_3$Co$_4$O$_9$, a layered thermoelectric cobaltite) indicates the existence of two magnetic transitions at $\sim$ 100 K and 400 - 600 K; the former is a transition from a paramagnetic state to an incommensurate ({\sf IC}) spin density wave ({\sf SDW}) state. The anisotropic behavior of zero-field $\mu^+$SR spectra at 5 K suggests that the {\sf IC-SDW} propagates in the $a$-$b$ plane, with oscillating moments directed along the c-axis; also the {\sf IC-SDW} is found to exist not in the [Ca$_2$CoO$_3$] subsystem but in the [CoO$_2$] subsystem. In addition, it is found that the long-range {\sf IC-SDW} order completes below $\sim$ 30 K, whereas the short-range order appears below 100 K. The latter transition is interpreted as a gradual change in the spin state of Co ions %% at temperatures above 400 K. These two magnetic transitions detected by $\mu^+$SR are found to correlate closely with the transport properties of [Ca$_2$CoO$_3$]$_{0.62}$[CoO$_2$].Comment: 7 pages, 8 figures. to be appeared in Phys. Rev.

Physical properties of misfit-layered (Bi,Pb)-Sr-Co-O system: Effect of hole doping into triangular lattice formed by low-spin Co ions

Pb-doping effect on physical properties of misfit-layered (Bi,Pb)-Sr-Co-O system, in which Co ions form a two-dimensional triangular lattice, was investigated in detail by electronic transport, magnetization and specific-heat measurements. Pb doping enhances the metallic behavior, suggesting that carriers are doped. Pb doping also enhances the magnetic correlation in this system and increases the magnetic transition temperature. We found the existence of the short-range magnetic correlation far above the transition temperature, which seems to induce the spin-glass state coexisting with the ferromagnetic long-range order at low temperatures. Specific-heat measurement suggests that the effective mass of the carrier in (Bi,Pb)-Sr-Co-O is not enhanced so much as reported in NaCo${}_2$O${}_4$. Based on these experimental results, we propose a two-bands model which consists of narrow $a_{1g}$ and rather broad $e'{}_g$ bands. The observed magnetic property and magnetotransport phenomena are explained well by this model

An Event-Related fMRI Study of Phonological Verbal Working Memory in Schizophrenia

Background: While much is known about the role of prefrontal cortex (PFC) in working memory (WM) deficits of schizophrenia, the nature of the relationship between cognitive components of WM and brain activation patterns remains unclear. We aimed to elucidate the neural correlates of the maintenance component of verbal WM by examining correct and error trials with event-related fMRI. Methodology/Findings: Twelve schizophrenia patients (SZ) and thirteen healthy control participants (CO) performed a phonological delayed-matching-to-sample-task in which a memory set of three nonsense words was presented, followed by a 6-seconds delay after which a probe nonsense word appeared. Participants decided whether the probe matched one of the targets, and rated the confidence of their decision. Blood-oxygen-level-dependent (BOLD) activity during WM maintenance was analyzed in relation to performance (correct/error) and confidence ratings. Frontal and parietal regions exhibited increased activation on correct trials for both groups. Correct and error trials were further segregated into true memory, false memory, guess, and true error trials. True memory trials were associated with increased bilateral activation of frontal and parietal regions in both groups but only CO showed deactivation in PFC. There was very little maintenancerelated cortical activity during guess trials. False memory was associated with increased left frontal and parietal activation in both groups. Conclusion: These findings suggest that a wider network of frontal and parietal regions support WM maintenance in correct trials compared with error trials in both groups. Furthermore, a more extensive and dynamic pattern of recruitment of the frontal and parietal networks for true memory was observed in healthy controls compared with schizophrenia patients. These results underscore the value of parsing the sources of memory errors in fMRI studies because of the non-linear nature of the brain-behavior relationship, and suggest that group comparisons need to be interpreted in more specific behavioral contexts

Bistable, Irregular Firing and Population Oscillations in a Modular Attractor Memory Network

Attractor neural networks are thought to underlie working memory functions in the cerebral cortex. Several such models have been proposed that successfully reproduce firing properties of neurons recorded from monkeys performing working memory tasks. However, the regular temporal structure of spike trains in these models is often incompatible with experimental data. Here, we show that the in vivo observations of bistable activity with irregular firing at the single cell level can be achieved in a large-scale network model with a modular structure in terms of several connected hypercolumns. Despite high irregularity of individual spike trains, the model shows population oscillations in the beta and gamma band in ground and active states, respectively. Irregular firing typically emerges in a high-conductance regime of balanced excitation and inhibition. Population oscillations can produce such a regime, but in previous models only a non-coding ground state was oscillatory. Due to the modular structure of our network, the oscillatory and irregular firing was maintained also in the active state without fine-tuning. Our model provides a novel mechanistic view of how irregular firing emerges in cortical populations as they go from beta to gamma oscillations during memory retrieval

The effect of peri-conception hyperglycaemia and the involvement of the hexosamine biosynthesis pathway in mediating oocyte and embryo developmental competence

The environment that the oocyte is exposed to during the peri-conception period can have a significant impact on oocyte developmental competence (the ability of the oocyte to support fertilisation and subsequent embryo development) and the long-term health of the resulting offspring. This is particularly true for maternal hyperglycaemia. While maternal hyperglycaemia during early pregnancy through term development has been extensively studied, the effects on the oocyte itself, and the underlying mechanisms, remain largely unknown. There is increasing evidence, however, for the role of the fuel-sensing hexosamine biosynthesis pathway in mediating the effects of hyperglycaemia in many different cell types. In this review, we will focus on the reproductive consequences of maternal hyperglycaemia during the peri-conceptual period and the role of the hexosamine pathway in mediating these processes.Laura A. Frank, Melanie L. Sutton-McDowall, Robert B. Gilchrist, and Jeremy G. Thompso

Effect of varying glucose and glucosamine concentration in vitro on mouse oocyte maturation and developmental competence

Published online: 7 November 2012The effects of hyper- and hypo-glycaemic conditions during the in vitro maturation of mouse cumulus–oocyte complexes on developmental competence were examined, with an emphasis on the role of the hexosamine biosynthesis pathway. A low (1 mM) glucose concentration achieved optimal oocyte competence (3-fold higher blastocyst development rate compared with high (30 mM) glucose, P < 0.05). In addition, glucose supplementation during only the first hour after release from the follicle was necessary and sufficient to support oocyte maturation and embryo development to the blastocyst stage. Glucosamine (a known hyperglycaemic mimetic and specific activator of the hexosamine pathway) was able to substitute for glucose during this first hour, indicating that flux through the hexosamine pathway is essential for oocyte competence. In the absence of glucose throughout the maturation period, glucosamine was not able to increase developmental competence, and at higher concentrations (2.5 and 5 mM) had a detrimental effect on MII and blastocyst development rates, compared with controls (P < 0.05). These experiments underscore the importance of glucose metabolic pathways during in vitro maturation and support the concept that excess flux through the hexosamine pathway has detrimental consequences.L. A. Frank, M. L. Sutton-McDowall, D. L. Russell, X. Wang, D. K. Feil, R. B. Gilchrist, and J. G. Thompso

TALEN Targeting of a novel safe-harbor in the <i>CLYBL</i> gene.

<p>(A) Sequence of CLYBL-TALEN target site at intron 2 of <i>CLYBL</i>. Exon numbers are indicated in the boxes of genomic locus. Bold fonts indicate TALEN binding sequences: left CLYBL-TALEN binds 5’-CTTACCCTTCTCCCATT; right CLYBL-TALEN binds 5’-CCCAAAATATATTTAT. Blue arrows indicate the primers for NHEJ assay. (B) Capillary electrophoresis plot from T7E1 assay indicates that our CLYBL TALENs have ~25% NHEJ efficiency based on the calculation: % gene modification = 100 × (1 − (1 − fraction cleaved)1/2), where fraction cleaved = T7E1 cut/(T7E1cut+uncut). Red arrows indicate T7E1 cleaved bands, blue arrow indicates uncut PCR band. (C) CLYBL TALEN activity estimated by targeted amplicon sequencing confirmed 25% (12 alleles out of 48) gene editing efficiency. Blue fonts are TALEN binding sequence. (D and F) Schematics of gene targeting at <i>CLYBL</i> safe-harbor on Chr. 13. The donors shown have the same reporter cassettes as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116032#pone.0116032.g001" target="_blank">Fig. 1C and 1E</a>, including insulator-flanked CAG-copGFP or CAG-iCLHN, except that <i>CLYBL</i> homology arms were used and pC13N-iCAG.cGFP has neomycin resistant gene (Neo) instead of Puro. Red lines indicate CLYBL probe used with AvrII digestion in Southern blot analysis. (E and G) Southern blots of pC13P-iCLHN targeted (E) and pC13N-iCAG.cGFP targeted (G) NCRM5 iPSC clones. Because the same position of AvrII sites in both donors and the ability of CLYBL probe to recognize WT, TI and RI, WT band is 5.4kb due to two AvrII sites in intron 2, TI band is 3.2kb due to donor-introduced AvrII site, and any other additional bands are RI. Clones with 1TI-only are indicated in red numbers; clones with 2TI-only are indicated in green numbers. Clone “C” indicate the control untargeted cells.</p

CLYBL safe-harbor enables heightened expression of transgenes.

<p>(A) Oregon green stained human iPSC clones with Nanoluc-HaloTag integrated in the <i>AAVS1</i> (AAVS1-iCLHN) or the <i>CLYBL</i> (CLYBL-iCLHN) safe-harbor bi-allelically without RI. Scale bar = 400 μm. (B) Comparison of HaloTag expression between <i>AAVS1</i> (AAVS1-iCLHN) and <i>CLYBL</i> (CLYBL-iCLHN) targeted NCRM5 iPSC clones using Oregon green (OG) ligand staining and flow cytometry. Y-axis = mean fluorescence intensity (MFI). Error bar = S.E.M. N = 3 (C) Nanoluc activity comparison of bi-allelically targeted AAVS1-iCLHN or CLYBL-iCLHN clones with untargeted NCRM5 control iPSCs. Y-axis is relative luciferase unit (RLU). X-axis is cell number. Data shown are the averages of 3 repeated measurements of three AAVS1-iCLHN clones, three CLYBL-iCLHN clones and one parental NCRM5 clone. Error bar = S.E.M. (E) Representative fluorescent images of CAG-driven copGFP expression in <i>AAVS1</i> (NCRM5-AS1-iCAGcGFP) or <i>CLYBL</i> (NCRM5-C13-iCAGcopGFP) targeted iPSC clones. Scale bar = 400 μm. (F) Quantitative comparison of copGFP expression between mono-allelically AAVS1 targeted (AAVS1-cGFP) and CLYBL targeted (CLYBL-cGFP) clones. Y-axis = MFI. Error bar = S.E.M. N = 2.</p

Safe-harbor targeting in human NSCs.

<p>(A) Southern analysis of Nanoluc-HaloTag (iCLHN) or tdTomato (iCAGTom) targeted NCRM1NSC or H9NSC at <i>AAVS1</i> or <i>CLYBL</i> locus using SphI or AvrII digestion, respectively. iPSCs with single TI of iCLHN at <i>AAVS1</i> allele were used as control. AAVS1 or CLYBL probes used to detect integrations at each safe-harbor are the same as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116032#pone.0116032.g004" target="_blank">Fig. 4</a>. Compared to the control, NCRM1NSC-AS1-iCLHN shows total loss of wild-type band (WT), indicating that all the cells in the polyclonal NSCs have bi-allelic TI at <i>AAVS1</i> locus. NCRM1NSCs or H9NSCs targeted by iCAGTom at <i>AAVS1</i> (AS1), and H9NSCs targeted by iCAGTom at <i>CLYBL</i> (C13) are estimated to have 44%-90% cells correctly targeted without random integrations (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116032#pone.0116032.s006" target="_blank">S6 Fig</a>.). Asterisk indicates additional RI. (B) Phase, HaloTag fluorescence (stained by Oregon green) and Nanoluc luminescence (pseudo-colored red) images of NCRM1NSC-AS1-iCLHN showed ~100% targeted NSCs express Nanoluc-HaloTag. (C and D) Limiting dilution-derived clones of dual safe-harbor targeted NSCs, NCRM1NSC-AS1Tom-C13GFP, were confirmed by Southern using AAVS1 probe/SphI digestion and CLYBL probe/BamHI digestion as indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116032#pone.0116032.g004" target="_blank">Fig. 4A</a>. BamHI digestion generates a 11.2kb band due to TI at CLYBL, compared to 4.4kb for WT allele. Note that clone 2, 3, 7 and 8 have bi-allelic <i>AAVS1</i> TI and mono-allelic <i>CLYBL</i> TI plus an additional RI. Asterisk indicates additional RI. Lane C is control NCRM1NSC. (E and F) Fluorescent images of undifferentiated (E) and differentiated (F) NCRM1NSC-AS1Tom-C13GFP clone 3. MAP2+ committed neurons showed persistent tdTomato and copGFP expression. Nuclei were stained by DAPI. Scale bar = 400 μm.</p