Simulating Cortical Feedback Modulation as Changes in Excitation and Inhibition in a Cortical Circuit Model.

Cortical feedback pathways are hypothesized to distribute context-dependent signals during flexible behavior. Recent experimental work has attempted to understand the mechanisms by which cortical feedback inputs modulate their target regions. Within the mouse whisker sensorimotor system, cortical feedback stimulation modulates spontaneous activity and sensory responsiveness, leading to enhanced sensory representations. However, the cellular mechanisms underlying these effects are currently unknown. In this study we use a simplified neural circuit model, which includes two recurrent excitatory populations and global inhibition, to simulate cortical modulation. First, we demonstrate how changes in the strengths of excitation and inhibition alter the input-output processing responses of our model. Second, we compare these responses with experimental findings from cortical feedback stimulation. Our analyses predict that enhanced inhibition underlies the changes in spontaneous and sensory evoked activity observed experimentally. More generally, these analyses provide a framework for relating cellular and synaptic properties to emergent circuit function and dynamic modulation

Current knowledge and recent advances in understanding metabolism of the model cyanobacterium Synechocystis sp. PCC 6803

Cyanobacteria are key organisms in the global ecosystem, useful models for studying metabolic and physiological processes conserved in photosynthetic organisms, and potential renewable platforms for production of chemicals. Characterising cyanobacterial metabolism and physiology is key to understanding their role in the environment and unlocking their potential for biotechnology applications. Many aspects of cyanobacterial biology differ from heterotrophic bacteria. For example, most cyanobacteria incorporate a series of internal thylakoid membranes where both oxygenic photosynthesis and respiration occur, while CO2 fixation takes place in specialised compartments termed carboxysomes. In this review, we provide a comprehensive summary of our knowledge on cyanobacterial physiology and the pathways in Synechocystis sp. PCC 6803 (Synechocystis) involved in biosynthesis of sugar-based metabolites, amino acids, nucleotides, lipids, cofactors, vitamins, isoprenoids, pigments and cell wall components, in addition to the proteins involved in metabolite transport. While some pathways are conserved between model cyanobacteria, such as Synechocystis, and model heterotrophic bacteria like Escherichia coli, many enzymes and/or pathways involved in the biosynthesis of key metabolites in cyanobacteria have not been completely characterised. These include pathways required for biosynthesis of chorismate and membrane lipids, nucleotides, several amino acids, vitamins and cofactors, and isoprenoids such as plastoquinone, carotenoids, and tocopherols. Moreover, our understanding of photorespiration, lipopolysaccharide assembly and transport, and degradation of lipids, sucrose, most vitamins and amino acids, and heme, is incomplete. We discuss tools that may aid characterisation of cyanobacterial metabolism, notably CyanoSource, a barcoded library of targeted Synechocystis mutants, which will significantly accelerate characterisation of individual proteins

Servant Leadership and its Relationships with Core Self-Evaluation and Job Satisfaction

Servant leadership is a growing topic in the leadership literature. Our study considered servant leadership’s relationship to two outcomes, core self-evaluation and job satisfaction. The former is particularly noteworthy because if servant leadership predicts core self-evaluation this would confirm that servant leadership affects important changes in employees as people, a central tenet of servant leadership. In addition, if servant leadership predicts core self-evaluation, this could add to the question of whether core self-evaluation is a non-changeable personality trait or is potentially malleable. We conducted a field study of three firms and found that servant leadership predicts both core self-evaluation and job satisfaction, and that core self-evaluation also predicts job satisfaction. This study contributes to servant leadership, and in general to values-based leadership, by observing a predictive relationship to core self-evaluation, which potentially adds new information about the impact servant leadership can have on individuals. This study confirms the findings of previous authors who found that servant leadership predicts job satisfaction

Characterisation of and T cell responses to the P91A tumour minus antigen.

The P91A tumour minus (tum-) antigen is a tumour specific transplantation antigen expressed on the P815 derivative cell line P91. The tumour minus form of the P91A protein has a single amino acid substitution in comparison to the wild-type protein due to a single base change in the P91A tum-gene. As a result of this amino acid substitution a unique H2-Ld binding peptide is generated and recognised in complex with H2-Ld by CD8+ cytotoxic T cells. P91A transgenic DBA/2 mice have been previously generated. Transgenic and non-transgenic mice differ only in expression of the P91A epitope. P91A peptide specific T cell responses have been examined in P91A transgenic and non-transgenic mice. T cells responsive to low concentrations of P91A peptide are present in non-transgenic mice while high concentrations of peptide are required to elicit equivalent proliferative responses in P91A transgenic mice. These results suggest that high affinity P91A specific T cells may have been deleted in P91A transgenic mice. P91A specific T cell clones have been generated from P91A transgenic and non-transgenic mice and their T cell receptor usage and sequence examined. Where possible this data has been correlated with recognition of the H2- Ld-P91A peptide complex. To further evaluate the interaction between P91A specific T cells and the P91A epitope the exact nature of the naturally processed P91A epitope has been determined and MHC and TCR contact residues defined. The P91A epitope is an octamer peptide which binds to Ld in the absence of consensus binding motif residues. Finally, using a series of P91A based minigenes evidence has been gained which suggests that the P91A epitope can be generated from P91A protein fragments which are targeted to the endoplasmic reticulum