Picturing Cities : The Photobook as Urban Narrative

What is a photobook? And how can we assess its historical and cultural re-levance for the representation of cities? The terms ‘photographic book’ and ‘picture book’ refer to various illustrated publications, with or without text, in which photographic images play a key role. Often resulting from the col-laboration between photographers, editors and graphic designers, they are intended to build visual narratives on specific places or subjects. Throughout its history, this versatile form of publication has allowed photographers to depict urban environments in widely different ways. Although the photobo-ok has been integral to the construction of urban narratives since the early-twentieth century, its significance for the experience and perception of cities has so far been rarely investigated. Picturing Cities addresses this gap by mapping the shifting nature and function of photobooks onto the history of urban representation. This collection of essays from Europe and the Ameri-cas illustrates a broad range of aesthetic attitudes as well as analytical ap-proaches to Western cities expressed through photobooks. The anthology, stemming from a conference session chaired by the editors, focuses on the photobook as a form of urban narrative: a tool that has been deployed to read, analyse and interpret cities through curated sequences of images, of-ten in conjunction with literary or critical texts. It opens up a multidisciplinary field of research with the potential to expand into further geographical and cultural areas

Quantum paradigms in psychopathology: multiscale investigations from biomolecular qubits to the brain, and its pathological states

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Alteration of lipid bilayer mechanics by volatile anesthetics: insights from μs-long molecular dynamics simulations

Very few drugs in clinical practice feature the chemical diversity, narrow therapeutic window, unique route of administration, and reversible cognitive effects of volatile anesthetics. The correlation between their hydrophobicity and their potency and the increasing amount of evidence suggesting that anesthetics exert their action on transmembrane proteins, justifies the investigation of their effects on phospholipid bilayers at the molecular level, given the strong functional and structural link between transmembrane proteins and the surrounding lipid matrix. Molecular dynamics simulations of a model lipid bilayer in the presence of ethylene, desflurane, methoxyflurane, and the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (also called F6 or 2N) at different concentrations highlight the structural consequences of VA partitioning in the lipid phase, with a decrease of lipid order and bilayer thickness, an increase in overall lipid lateral mobility and area-per-lipid, and a marked reduction in the mechanical stiffness of the membrane, that strongly correlates with the compounds' hydrophobicity

Prediction of Protein–Protein Interactions Between Alsin DH/PH and Rac1 and Resulting Protein Dynamics

Alsin is a protein of 1,657 amino acids known for its crucial role in vesicular trafficking in neurons thanks to its ability to interact with two guanosine triphosphatases, Rac1 and Rab5. Evidence suggests that Rac1 can bind Alsin central region, composed by a Dbl Homology (DH) domain followed by a Pleckstrin Homology (PH) domain, leading to Alsin relocalization. However, Alsin three-dimensional structure and its relationship with known biological functions of this protein are still unknown. In this work, a homology model of the Alsin DH/PH domain was developed and studied through molecular dynamics both in the presence and in the absence of its binding partner, Rac1. Due to different conformations of DH domain, the presence of Rac1 seems to stabilize an open state of the protein, while the absence of its binding partner results in closed conformations. Furthermore, Rac1 interaction was able to reduce the fluctuations in the second conserved region of DH motif, which may be involved in the formation of a homodimer. Moreover, the dynamics of DH/PH was described through a Markov State Model to study the pathways linking the open and closed states. In conclusion, this work provided an all-atom model for the DH/PH domain of Alsin protein; moreover, molecular dynamics investigations suggested underlying molecular mechanisms in the signal transduction between Rac1 and Alsin, providing the basis for a deeper understanding of the whole structure–function relationship for Alsin protein

Deformation pattern in vibrating microtubule: Structural mechanics study based on an atomistic approach

The mechanical properties of microtubules are of great importance for understanding their biological function and for applications in artificial devices. Although microtubule mechanics has been extensively studied both theoretically and experimentally, the relation to its molecular structure is understood only partially. Here, we report on the structural analysis of microtubule vibration modes calculated by an atomistic approach. Molecular dynamics was applied to refine the atomic structure of a microtubule and a C α elastic network model was analyzed for its normal modes. We mapped fluctuations and local deformations up to the level of individual aminoacid residues. The deformation is mode-shape dependent and principally different in α-tubulins and β-tubulins. Parts of the tubulin dimer sequence responding specifically to longitudinal and radial stress are identified. We show that substantial strain within a microtubule is located both in the regions of contact between adjacent dimers and in the body of tubulins. Our results provide supportive evidence for the generally accepted assumption that the mechanics of microtubules, including its anisotropy, is determined by the bonds between tubulins

In silico investigation of molecular interactions of Volatile Anesthetics: Effects on phospholipid membranes and subcellular targets

The ability of anesthetics to reversibly suppress consciousness must reside in the effects exerted onto specific molecular tar- gets. Interactions between Volatile Anesthetics and the phospholipid mem- brane as well as intracellular tubulin, were investigated using Computational Molecular Modelling, which showed rapid ligand partitioning inside the membrane and significant effects on the mechanical char- acteristics thereof, while transient binding locations have been found on the tubulin dimer

Aminoacid substitutions in the glycine zipper affect the conformational stability of amyloid beta fibrils

The aggregation of amyloid-beta peptides is associated with the pathogenesis of Alzheimer’s disease. The hydrophobic core of the amyloid beta sequence contains a GxxxG repeated motif, called glycine zipper, which involves crucial residues for assuring stability and promoting the process of fibril formation. Mutations in this motif lead to a completely different oligomerization pathway and rate of fibril formation. In this work, we have tested G33L and G37L residue substitutions by molecular dynamics simulations. We found that both protein mutations may lead to remarkable changes in the fibril conformational stability. Results suggest the disruption of the glycine zipper as a possible strategy to reduce the aggregation propensity of amyloid beta peptides. On the basis of our data, further investigations may consider this key region as a binding site to design/discover novel effective inhibitors. Communicated by Ramaswamy H. Sarma

Insights into the interaction dynamics between volatile anesthetics and tubulin through computational molecular modelling

General anesthetics, able to reversibly suppress all conscious brain activity, have baffled medical science for decades, and little is known about their exact molecular mechanism of action. Given the recent scientific interest in the exploration of microtubules as putative functional targets of anesthetics, and the involvement thereof in neurodegenerative disorders, the present work focuses on the investigation of the interaction between human tubulin and four volatile anesthetics: ethylene, desflurane, halothane and methoxyflurane. Interaction sites on different tubulin isotypes are predicted through docking, along with an estimate of the binding affinity ranking. The analysis is expanded by Molecular Dynamics simulations, where the dimers are allowed to freely interact with anesthetics in the surrounding medium. This allowed for the determination of interaction hotspots on tubulin dimers, which could be linked to different functional consequences on the microtubule architecture, and confirmed the weak, Van der Waals-type interaction, occurring within hydrophobic pockets on the dimer. Both docking and MD simulations highlighted significantly weaker interactions of ethylene, consistent with its far lower potency as a general anesthetic. Overall, simulations suggest a transient interaction between anesthetics and microtubules in general anesthesia, and contact probability analysis shows interaction strengths consistent with the potencies of the four compounds

Correction: Electro-acoustic behavior of the mitotic spindle: A semi-classical coarse-grained model (PLoS ONE (2014) 9:1 (e86501) DOI: 10.1371/journal.pone.0086501)

There are errors in the values reported for parameters a, b, c, and V in Table 1. Please see the correct Table 1 here. [Table Preasented]. There is an error in the equation in the third sentence in the “The arrangement of microtubules” subsection of the Models section. The equation describing the distance from the origin of the coordinate system for MTOC placement on the x-axis is incorrect. Please see the correct equation here: [Formola Presented]. There is an error in the Eq (6) in the “Calculation of the intensity of the electric field” subsection of the Models section. Please see the correct Eq (6) here: [Formola Presented]. There is an error in the Eq (7) in the “Calculation of the intensity of the electric field” subsection of the Models section. Please see the correct Eq (7) here: [Formola Presented]. The authors confirm that the code used in the modelling do not contain the errors in parameters and equations, which affect only the description of the models. The results and conclusions are therefore unaffected by these corrections to the reporting of the methodology. There are errors in the scale of the y-axis shown for the bottom panel of Fig 10. Please see the correct Fig 10 here.[Figure Presented]

The role of structural polymorphism in driving the mechanical performance of the alzheimer's beta amyloid fibrils

Alzheimer's Disease (AD) is related with the abnormal aggregation of amyloid β-peptides Aβ1-40 and Aβ1-42, the latter having a polymorphic character which gives rise to U- or S-shaped fibrils. Elucidating the role played by the nanoscale-material architecture on the amyloid fibril stability is a crucial breakthrough to better understand the pathological nature of amyloid structures and to support the rational design of bio-inspired materials. The computational study here presented highlights the superior mechanical behavior of the S-architecture, characterized by a Young's modulus markedly higher than the U-shaped architecture. The S-architecture showed a higher mechanical resistance to the enforced deformation along the fibril axis, consequence of a better interchain hydrogen bonds' distribution. In conclusion, this study, focusing the attention on the pivotal multiscale relationship between molecular phenomena and material properties, suggests the S-shaped Aβ1-42 species as a target of election in computational screen/design/optimization of effective aggregation modulators