Anti-infectives in Drug Delivery-Overcoming the Gram-Negative Bacterial Cell Envelope.

Infectious diseases are becoming a major menace to the state of health worldwide, with difficulties in effective treatment especially of nosocomial infections caused by Gram-negative bacteria being increasingly reported. Inadequate permeation of anti-infectives into or across the Gram-negative bacterial cell envelope, due to its intrinsic barrier function as well as barrier enhancement mediated by resistance mechanisms, can be identified as one of the major reasons for insufficient therapeutic effects. Several in vitro, in silico, and in cellulo models are currently employed to increase the knowledge of anti-infective transport processes into or across the bacterial cell envelope; however, all such models exhibit drawbacks or have limitations with respect to the information they are able to provide. Thus, new approaches which allow for more comprehensive characterization of anti-infective permeation processes (and as such, would be usable as screening methods in early drug discovery and development) are desperately needed. Furthermore, delivery methods or technologies capable of enhancing anti-infective permeation into or across the bacterial cell envelope are required. In this respect, particle-based carrier systems have already been shown to provide the opportunity to overcome compound-related difficulties and allow for targeted delivery. In addition, formulations combining efflux pump inhibitors or antimicrobial peptides with anti-infectives show promise in the restoration of antibiotic activity in resistant bacterial strains. Despite considerable progress in this field however, the design of carriers to specifically enhance transport across the bacterial envelope or to target difficult-to-treat (e.g., intracellular) infections remains an urgently needed area of improvement. What follows is a summary and evaluation of the state of the art of both bacterial permeation models and advanced anti-infective formulation strategies, together with an outlook for future directions in these fields

Increased Cell Proliferation and Mucocyte Density in the Sea Anemone Aiptasia pallida Recovering from Bleaching

Recovery of coral after bleaching episodes is a critical period for the health of the reef ecosystem. While events such as symbiont (genus Symbiodinium) shifting/shuffling or tissue apoptosis have been demonstrated to occur following bleaching, little is known concerning tissue recovery or cell proliferation. Here, we studied the sea anemone Aiptasia pallida exposed to a transient elevation of water temperature combined with high illumination (33°C and 1900 μmolphotons.m.s for 30h). Following such treatment bleached anemones showed a significant reduction of their Symbiodinium density. Cell proliferation in the ectodermis and gastrodermis was determined by assessing the densities of cells labeled with a thymidine analogue (EdU). Cell proliferation significantly increased during the first day following stress in both tissue types. This increased cell proliferation returned to pre-stress values after one week. Although cell proliferation was higher in the ectodermis in absence of stress, it was relatively more pronounced in the gastrodermis of stressed anemones. In addition, the ratio of ectodermal mucocytes significantly increased three weeks after induced stress. These results suggest that thermal/photic stress coupled with the loss of the symbionts is able to enhance cell proliferation in both gastrodermis and ectodermis of cnidarians. While new cells formed in the gastrodermis are likely to host new Symbiodinium, the fate of new cells in the ectodermis was only partially revealed. Some new ectodermal cells may, in part, contribute to the increased number of mucocytes which could eventually help strengthen the heterotrophic state until restoration of the symbiosis

Alma Mater: 2015/Pavasaris

Proceedings of the 2nd AtMol European Workshop.Quantum coherence and entanglement give resources to enhance the capabilities of computers well beyond those achievable by present-day or even future classical devices. Quantum information processing can be carried out via a combination of two elementary logic operations: unitary rotations of individual qubits and quantum-gate operations that involve at least two coupled qubits. An outstanding challenge for science and technology is to find suitable realizations of these basic elements. In recent years, magnetic molecular clusters have become candidates to implement the quantum computer hardware. Here, we summarize some of the strategies that have been followed to design and synthesize molecular spin qubits and quantum gates. In particular, we show that molecular clusters containing two Tb3+ ions meet all ingredients required to implement a CNOT quantum logic gate. The definition of control and target qubits is based on the strong magnetic anisotropy and the magnetic inequivalence of the two ions, which can be achieved by chemically engineering dissimilar coordination spheres. The magnetic asymmetry also provides a method to realize a SWAP gate in the same cluster. The synthesis of related molecular structures enables a vast choice of quantum-gate designs. Chemically engineered molecular quantum gates can therefore open promising avenues for the realization of scalable quantum computing architectures.This work was partly funded by grants MAT2009–13977-C03 (MOLCHIP), CTQ2009–06959, FIS2008–01240 and FIS2009–13364-C02, from the Spanish MICINN and the Consolider-Ingenio project on molecular nanoscience. Funding from the European Research Council Starting Grant FuncMolQIP (to GA) is also acknowledged. G. A. acknowledges Generalitat de Catalunya for the ICREA Academia prize 2008Peer reviewe

Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics

Neuroimaging investigations of autism spectrum disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread atypicalities in brain regions involved in social behavior and other core ASD-related behavioral deficits. More recent advances in MR-neuroimaging methods allow for quantification of brain connectivity using diffusion tensor imaging, functional connectivity, and graph theoretic methods. These newer techniques have moved the field toward a systems-level understanding of ASD etiology, integrating functional and structural measures across distal brain regions. Neuroimaging findings in ASD as a whole have been mixed and at times contradictory, likely due to the vast genetic and phenotypic heterogeneity characteristic of the disorder. Future longitudinal studies of brain development will be crucial to yield insights into mechanisms of disease etiology in ASD sub-populations. Advances in neuroimaging methods and large-scale collaborations will also allow for an integrated approach linking neuroimaging, genetics, and phenotypic data