Synthetic Organic Design for Solar Fuel Systems.

From the understanding of biological processes and metalloenzymes to the development of inorganic catalysts, electro- and photocatalytic systems for fuel generation have evolved considerably during the last decades. Recently, organic and hybrid organic systems have emerged to challenge the classical inorganic structures through their enormous chemical diversity and modularity that led earlier to their success in organic (opto)electronics. This Minireview describes recent advances in the design of synthetic organic architectures and promising strategies toward (solar) fuel synthesis, highlighting progress on materials from organic ligands and chromophores to conjugated polymers and covalent organic frameworks

The compositional and evolutionary logic of metabolism

Metabolism displays striking and robust regularities in the forms of modularity and hierarchy, whose composition may be compactly described. This renders metabolic architecture comprehensible as a system, and suggests the order in which layers of that system emerged. Metabolism also serves as the foundation in other hierarchies, at least up to cellular integration including bioenergetics and molecular replication, and trophic ecology. The recapitulation of patterns first seen in metabolism, in these higher levels, suggests metabolism as a source of causation or constraint on many forms of organization in the biosphere. We identify as modules widely reused subsets of chemicals, reactions, or functions, each with a conserved internal structure. At the small molecule substrate level, module boundaries are generally associated with the most complex reaction mechanisms and the most conserved enzymes. Cofactors form a structurally and functionally distinctive control layer over the small-molecule substrate. Complex cofactors are often used at module boundaries of the substrate level, while simpler ones participate in widely used reactions. Cofactor functions thus act as "keys" that incorporate classes of organic reactions within biochemistry. The same modules that organize the compositional diversity of metabolism are argued to have governed long-term evolution. Early evolution of core metabolism, especially carbon-fixation, appears to have required few innovations among a small number of conserved modules, to produce adaptations to simple biogeochemical changes of environment. We demonstrate these features of metabolism at several levels of hierarchy, beginning with the small-molecule substrate and network architecture, continuing with cofactors and key conserved reactions, and culminating in the aggregation of multiple diverse physical and biochemical processes in cells.Comment: 56 pages, 28 figure

Genetic dissection of circuits underlying the modular structure of the Superior Colliculus

In order to successfully interact with the environment, animals need to produce accurate movements towards specific positions in space. A crucial region of the brain that guides such goal-oriented movements is the superior colliculus (SC), an evolutionary conserved structure of the midbrain. While several lines of research in different model organisms have confirmed that the SC contributes to the initiation of orienting movements, how functionally distinct neuronal groups within the SC are organized to support the production of such motor outputs is poorly understood. One of the reasons why the intrinsic circuit organization of the SC remains elusive is the lack of genetic characterization of the neuronal populations of the motor SC. Here, we performed RNAseq to screen for genetic markers for neuronal subpopulations in the motor SC. We identified a transcription factor, Pitx2, which is exclusively expressed in a subpopulation of glutamatergic neurons in the motor domain of the SC. Strikingly, this population of neurons displays a non-homogenous distribution within the motor layer of the SC, being organised in clusters along the mediolateral and anteroposterior axis. We mapped the pre-synaptic network and the post-synaptic targets of Pitx2ON neurons, unveiling that this modular population receives direct inputs from motor and sensory cortical regions, as well as several midbrain nuclei involved in movement control, and sends projection along the cephalomotor pathway. We then asked whether these modules may act as functional units, each integrating multimodal sensory information and encoding a specific feature of head movement, the main ethologically relevant orienting behaviour in rodents. Optogenetic activation of this modular population in freely moving animals produced a stereotyped, robust head motion characterised by a pronounced quantal nature; furthermore, the amplitude of the elicited head movement varied based on the modular unit activated. Our results suggest that distinct clusters of genetically defined neurons produce head displacement along a characteristic vector. In conclusion, we found that a population of premotor neurons in the SC is organised in a modular conformation and we suggest that such modularity may represent a physical implementation of a discontinuous motor map for orienting movements encoded in the mouse SC. Our work complements previous observations of periodicity in SC circuitry, as well as its afferent and efferent systems. Exploiting the genetic toolkit available in the mouse, our work begins to address the functional relevance of this modularity and paves the way for future experiments to investigate principles of sensorimotor integration in SC circuits.MR

Combined scanning probe microscopy and x-ray scattering instrument for in situ catalysis investigations

Catalysis and Surface Chemistr

Graph analysis of TMS–EEG connectivity reveals hemispheric differences following occipital stimulation

(1) Background: Transcranial magnetic stimulation combined with electroencephalography (TMS–EEG) provides a unique opportunity to investigate brain connectivity. However, possible hemispheric asymmetries in signal propagation dynamics following occipital TMS have not been investigated. (2) Methods: Eighteen healthy participants underwent occipital single-pulse TMS at two different EEG sites, corresponding to early visual areas. We used a state-of-the-art Bayesian estimation approach to accurately estimate TMS-evoked potentials (TEPs) from EEG data, which has not been previously used in this context. To capture the rapid dynamics of information flow patterns, we implemented a self-tuning optimized Kalman (STOK) filter in conjunction with the information partial directed coherence (iPDC) measure, enabling us to derive time-varying connectivity matrices. Subsequently, graph analysis was conducted to assess key network properties, providing insight into the overall network organization of the brain network. (3) Results: Our findings revealed distinct lateralized effects on effective brain connectivity and graph networks after TMS stimulation, with left stimulation facilitating enhanced communication between contralateral frontal regions and right stimulation promoting increased intra-hemispheric ipsilateral connectivity, as evidenced by statistical test (p < 0.001). (4) Conclusions: The identified hemispheric differences in terms of connectivity provide novel insights into brain networks involved in visual information processing, revealing the hemispheric specificity of neural responses to occipital stimulation

Reshaping cortical connectivity in traumatic spinal cord injury: a novel effect of hyperbaric oxygen therapy

Introduction: Spinal cord injuries (SCIs) represent a severe neuro-traumatic occurrence and an excruciating social burden. Though the hyperbaric oxygen (HBO2) has been credited as a first line therapeutic resource for SCIs, its mechanism of action in the spine is only partially known, while the impingement upon other areas of the nervous system deserves additional investigation. In this study we deem to describe a novel effect of HBO2 in a subject affected by SCI who, along with the clinical improvement, showed a reshaped connectivity in cortical sensory-motor areas. Case presentation: A 45 years male presenting severe sensory-motor symptoms following a spinal lesion partially involving the C1 segment was successfully treated with HBO2 cycles. After the dramatic improvement reflected by an excellent optimization of the single performances, it has been investigated whether this result would reveal not only an intrinsic effect upon the spinal cord, but also a better connectivity strength in sensory-motor cortical regions. The results obtained by implementing EEG recordings with EEGLAB auto regressive vector plugins indeed suggest a substantial reshaping of cortico-cortical connectivity after HBO2. Discussion: These results show a correlation between positive clinical evolution and a new modulation of cortical connectivity. Though further clinical investigations would clarify as to whether HBO2 might be directly or epiphenomenally involved in this aspect of the network architecture, our report suggests that a comparison between clinical results and the study of brain connectivity represent a holistic approach in investigating the physiopathology of SCIs and in monitoring the treatment

Quantitative dissection of the simple repression input–output function

We present a quantitative case study of transcriptional regulation in which we carry out a systematic dialogue between theory and measurement for an important and ubiquitous regulatory motif in bacteria, namely, that of simple repression. This architecture is realized by a single repressor binding site overlapping the promoter. From the theory point of view, this motif is described by a single gene regulation function based upon only a few parameters that are convenient theoretically and accessible experimentally. The usual approach is turned on its side by using the mathematical description of these regulatory motifs as a predictive tool to determine the number of repressors in a collection of strains with a large variation in repressor copy number. The predictions and corresponding measurements are carried out over a large dynamic range in both expression fold change (spanning nearly four orders of magnitude) and repressor copy number (spanning about two orders of magnitude). The predictions are tested by measuring the resulting level of gene expression and are then validated by using quantitative immunoblots. The key outcomes of this study include a systematic quantitative analysis of the limits and validity of the input–output relation for simple repression, a precise determination of the in vivo binding energies for DNA–repressor interactions for several distinct repressor binding sites, and a repressor census for Lac repressor in Escherichia coli