Decoding the activity of neuronal populations in macaque primary visual cortex

Visual function depends on the accuracy of signals carried by visual cortical neurons. Combining information across neurons should improve this accuracy because single neuron activity is variable. We examined the reliability of information inferred from populations of simultaneously recorded neurons in macaque primary visual cortex. We considered a decoding framework that computes the likelihood of visual stimuli from a pattern of population activity by linearly combining neuronal responses and tested this framework for orientation estimation and discrimination. We derived a simple parametric decoder assuming neuronal independence and a more sophisticated empirical decoder that learned the structure of the measured neuronal response distributions, including their correlated variability. The empirical decoder used the structure of these response distributions to perform better than its parametric variant, indicating that their structure contains critical information for sensory decoding. These results show how neuronal responses can best be used to inform perceptual decision-making

Rescue of splicing-mediated intron loss maximizes expression in lentiviral vectors containing the human ubiquitin C promoter.

Lentiviral vectors almost universally use heterologous internal promoters to express transgenes. One of the most commonly used promoter fragments is a 1.2-kb sequence from the human ubiquitin C (UBC) gene, encompassing the promoter, some enhancers, first exon, first intron and a small part of the second exon of UBC. Because splicing can occur after transcription of the vector genome during vector production, we investigated whether the intron within the UBC promoter fragment is faithfully transmitted to target cells. Genetic analysis revealed that more than 80% of proviral forms lack the intron of the UBC promoter. The human elongation factor 1 alpha (EEF1A1) promoter fragment intron was not lost during lentiviral packaging, and this difference between the UBC and EEF1A1 promoter introns was conferred by promoter exonic sequences. UBC promoter intron loss caused a 4-fold reduction in transgene expression. Movement of the expression cassette to the opposite strand prevented intron loss and restored full expression. This increase in expression was mostly due to non-classical enhancer activity within the intron, and movement of putative intronic enhancer sequences to multiple promoter-proximal sites actually repressed expression. Reversal of the UBC promoter also prevented intron loss and restored full expression in bidirectional lentiviral vectors

Do Different Neurons Age Differently? Direct Genome-Wide Analysis of Aging in Single Identified Cholinergic Neurons

Aplysia californica is a powerful experimental system to study the entire scope of genomic and epigenomic regulation at the resolution of single functionally characterized neurons and is an emerging model in the neurobiology of aging. First, we have identified and cloned a number of evolutionarily conserved genes that are age-related, including components of apoptosis and chromatin remodeling. Second, we performed gene expression profiling of different identified cholinergic neurons between young and aged animals. Our initial analysis indicates that two cholinergic neurons (R2 and LPl1) revealed highly differential genome-wide changes following aging suggesting that on the molecular scale different neurons indeed age differently. Each of the neurons tested has a unique subset of genes differentially expressed in older animals, and the majority of differently expressed genes (including those related to apoptosis and Alzheimer's disease) are found in aging neurons of one but not another type. The performed analysis allows us to implicate (i) cell specific changes in histones, (ii) DNA methylation and (iii) regional relocation of RNAs as key processes underlying age-related changes in neuronal functions and synaptic plasticity. These mechanisms can fine-tune the dynamics of long-term chromatin remodeling, or control weakening and the loss of synaptic connections in aging. At the same time our genomic tests revealed evolutionarily conserved gene clusters associated with aging (e.g., apoptosis-, telomere- and redox-dependent processes, insulin and estrogen signaling and water channels)

Conduction band tight-binding description for silicon applied to phosphorous donors

A tight-binding parametrization for silicon, optimized to correctly reproduce effective masses as well as the reciprocal space positions of the conduction-band minima, is presented. The reliability of the proposed parametrization is assessed by performing systematic comparisons between the descriptions of donor impurities in Si using this parametrization and previously reported ones. The spectral decomposition of the donor wavefunction demonstrates the importance of incorporating full band effects for a reliable representation, and that an incomplete real space description results from a truncated reciprocal space expansion as proposed within the effective mass theory.Comment: 4 pages, 3 figure

Long-term neurocognitive function of pediatric patients with severe combined immune deficiency (SCID): pre- and post-hematopoietic stem cell transplant (HSCT).

BACKGROUND:Hematopoietic stem cell transplantation (HSCT) is the only cure for patients with severe combined immunodeficiency (SCID). The purpose of this study was to evaluate long-term neurodevelopment of patients with SCID following myeloablative chemotherapy and HSCT. MATERIALS AND METHODS:Sixteen pediatric patients diagnosed with SCID were tested using the Bayley Scales of Infant Development and the validated Vineland Adaptive Behavior Scales (VABS) pre- and 1-year post-HSCT. Three years post-HSCT, there were 11 patients available for testing and four patients available 5 years post-HSCT. Patients greater than 3 years of age were administered the Wechsler Preschool and Primary Scale of Intelligence. Both raw scores and scaled scores were analyzed. RESULTS:There was a significant decrease 1 year post-HSCT in the Bayley Mental Developmental Index (MDI) [92.5 (pre) vs. 70.81 (1 year post), p < 0.0001] and the VABS [99.73 (pre) vs. 79.87 (1 year post), p = <0.0001]. There was a significant decrease over time in the MDI [95.00 (pre) vs. 72.64 (1 year post) vs. 71.82 (3 years post), p < 0.0001], but no significant change between 1 and 3 years post-HSCT. There was no change in the Bayley Psychomotor Development Scale (PDI) [82.4 (pre) vs. 84.8 (1 year post), p = 0.68]. The PDI scores decreased over time [86.29 (pre) vs. 86 (1 year post) vs. 74.14 (3 years post), p = 0.045]. Although there was a decrease in scaled scores, there was not a loss of skills. Analysis of raw scores showed that there was an increase in the raw test scores, which indicated that these children acquired developmental skills, but at a slower rate than normal infants and toddlers. Younger children had a more significant decrease in adaptive scores compared with older children. CONCLUSIONS:These findings may reflect the effects of the isolation and prolonged hospitalization that characterizes the immediate post-transplant period. Patients miss out on social interactions and learning opportunities that normally occur at their respective stages of development. These restrictions keep patients from acquiring developmentally appropriate cognitive skills as well as gross and fine motor developmental milestones. Longitudinal follow-up will be important to quantify acquisition of skills

Zearalenone-malonyl-glucosides as phase II metabolites in plant cell suspension cultures

Background and objectives Conjugation of mycotoxins in the phase II metabolism of plants results in modified mycotoxins such as glucosides and malonyl‐glucosides. However, malonyl‐glucosides have not yet been completely elucidated for zearalenone (ZEN). Thus, the aim of this study was to produce and isolate malonyl‐glucosides of ZEN for an unambiguous identification by NMR spectroscopy. Findings Zearalenone was incubated in plant cell suspension cultures of wheat, soy, and tobacco, and phase II metabolites were analyzed by using LC‐DAD‐MS, ‐HRMS, and NMR spectroscopy. Four main metabolites of ZEN were detected in the cell extracts and identified as two glucosides (attached in positions 14 and 16) and their 6´‐malonyl derivatives. Conclusions Zearalenone‐malonyl‐glucosides should be incorporated in future analyses of modified mycotoxins because of their potential relevance for food and feed safety. Significance and novelty For the first time, the structures of the two malonyl‐glucosides of ZEN were unambiguously identified by NMR spectroscopy after preparative isolation as 14‐O‐(6’‐O‐malonyl‐β‐D‐glucopyranosyl)ZEN and 16‐O‐(6’‐O‐malonyl‐β‐D‐glucopyranosyl)ZEN

Donor Electron Wave Functions for Phosphorus in Silicon: Beyond Effective Mass Theory

We calculate the electronic wave-function for a phosphorus donor in silicon by numerical diagonalisation of the donor Hamiltonian in the basis of the pure crystal Bloch functions. The Hamiltonian is calculated at discrete points localised around the conduction band minima in the reciprocal lattice space. Such a technique goes beyond the approximations inherent in the effective-mass theory, and can be modified to include the effects of altered donor impurity potentials, externally applied electro-static potentials, as well as the effects of lattice strain. Modification of the donor impurity potential allows the experimentally known low-lying energy spectrum to be reproduced with good agreement, as well as the calculation of the donor wavefunction, which can then be used to calculate parameters important to quantum computing applications.Comment: 10 pages, 5 figure

Superior lentiviral vectors designed for BSL-0 environment abolish vector mobilization.

Lentiviral vector mobilization following HIV-1 infection of vector-transduced cells poses biosafety risks to vector-treated patients and their communities. The self-inactivating (SIN) vector design has reduced, however, not abolished mobilization of integrated vector genomes. Furthermore, an earlier study demonstrated the ability of the major product of reverse transcription, a circular SIN HIV-1 vector comprising a single- long terminal repeat (LTR) to support production of high vector titers. Here, we demonstrate that configuring the internal vector expression cassette in opposite orientation to the LTRs abolishes mobilization of SIN vectors. This additional SIN mechanism is in part premised on induction of host PKR response to double-stranded RNAs comprised of mRNAs transcribed from cryptic transcription initiation sites around 3'SIN-LTR's and the vector internal promoter. As anticipated, PKR response following transfection of opposite orientation vectors, negatively affects their titers. Importantly, shRNA-mediated knockdown of PKR rendered titers of SIN HIV-1 vectors comprising opposite orientation expression cassettes comparable to titers of conventional SIN vectors. High-titer vectors carrying an expression cassette in opposite orientation to the LTRs efficiently delivered and maintained high levels of transgene expression in mouse livers. This study establishes opposite orientation expression cassettes as an additional PKR-dependent SIN mechanism that abolishes vector mobilization from integrated and episomal SIN lentiviral vectors

A theoretical investigation into the microwave spectroscopy of a phosphorus-donor charge-qubit in silicon: Coherent control in the Si:P quantum computer architecture

We present a theoretical analysis of a microwave spectroscopy experiment on a charge qubit defined by a P$_2^+$ donor pair in silicon, for which we calculate Hamiltonian parameters using the effective-mass theory of shallow donors. We solve the master equation of the driven system in a dissipative environment to predict experimental outcomes. We describe how to calculate physical parameters of the system from such experimental results, including the dephasing time, $T_2$, and the ratio of the resonant Rabi frequency to the relaxation rate. Finally we calculate probability distributions for experimentally relevant system parameters for a particular fabrication regime