Pin1 is a Prolyl Isomerase that catalyzes cis-trans isomerization of peptides with pSer/Thr-Pro motifs in many cell signaling proteins. This conformational switch is implicated in diseases. Pin1 activity is considered a target for therapeutic applications. Pin1 targets motifs by its N-terminal WW-binding domain. A C-terminal PPIase domain is responsible for catalysis. To understand how Pin1 coordinates its enzymatic activities, it is necessary to probe how the domains behave in the presence of substrates. Here, we used novel (Histone H1 and Sic1) and other existing peptides to characterize the dynamics of Pin1 and impact of substrate binding on inter-domain interactions. Pin1-peptide complexes have been used to show that peptide addition causes a conformational change in the two domains. 15N-relaxation data suggest that the flexibility of these domains depends on the substrate peptide We have constructed a hypothesis about which substrate residues may be important for conferring tight binding and inter-domain interactions.

A great deal of talent has been called upon over the past decade to try and understand the structure and the function of different types of foldases; as a result, a remarkable insight into how these enzymes work has been gained. Recently the main focus of research has begun to shift to unveiling the precise role of these folding catalysts in many different processes in which they are involved inside the cell. It is becoming increasingly clear that the cellular functions of foldases go far beyond accelerating the folding of proteins. This is undoubtedly an area where one can expect significant research efforts in the next few years. The present book summarises the current state of knowledge as to the structural and functional properties of four major types of foldases listed above. In structuring the material the author has sought to maintain a balance between historical development and current understanding, while also trying to look to the future and anticipate where the field is likely to move.

This special volume of Progress in Molecular Biology and Translational Science provides a current overview of how memory is processed in the brain. A broad range of topics are presented by leaders in the field, ranging from brain circuitry to synaptic plasticity to the molecular machinery that contributes to the brain's ability to maintain information across time. Memory systems in the prefrontal cortex, hippocampus and amygdala are considered as well. In addition, the volume covers recent contributions to our understanding of memory from in vivo imaging, optogenetic, electrophysiological, biochemical and molecular biological studies. Articles from world renowned experts in memory Covering topics from signaling, epigenetic, RNA translation to plasticity Methodological approaches include molecular and cellular, behavioral, electrophysiological, optogenetic and functional imaging

Fast inhibitory transmission exerts a powerful control on neuronal excitability and network oscillations thought to be associated with high cognitive functions. An alteration of inhibitory signaling is associated with major neurological and psychiatric disorders including epilepsy. Once released from presynaptic nerve terminals, GABA and glycine cross the synaptic cleft and bind to postsynaptic receptors localized in precise apposition to presynaptic release sites. The functional organization of inhibitory synapses consists in a dynamic process which relies on a number of highly specialized proteins that ensure the correct targeting, clustering, stabilization and subsequent fate of synaptic receptors. Among the proteins involved in this task, the tubulin-binding protein gephyrin plays a crucial role. Through its self-oligomerization properties, this protein forms hexagonal lattices that trap GABAA and glycine receptors and link them to the cytoskeleton. By directly interacting with cell-adhesion molecules of the neuroligin-neurexin families that connect presynaptic and postsynaptic neurons at synapses, gephyrin ensures a backward control of presynaptic signaling. In addition, changes in clusters size is dynamically regulated by lateral diffusion of neurotransmitter receptors between the synaptic and extrasynaptic compartments and by their interaction with synaptic scaffold proteins. The aim of this Research Topic (research articles and reviews) is to bring together experts on the cellular and molecular mechanisms regulating the appropriate assembly, location and function of pre and postsynaptic specializations at inhibitory synapses. A particular emphasis will be on the role of receptor trafficking in synaptic stabilization and plasticity.

The first edition of this publication was aimed at defining the current concepts of trauma induced coagulopathy by critically analyzing the most up-to-date studies from a clinical and basic science perspective. It served as a reference source for any clinician interested in reviewing the pathophysiology, diagnosis, and management of the coagulopathic trauma patient, and the data that supports it. By meticulously describing the methodology of most traditional as well as state of the art coagulation assays the reader is provided with a full understanding of the tests that are used to study trauma induced coagulopathy. With the growing interest in understanding and managing coagulation in trauma, this second edition has been expanded to 46 chapters from its original 35 to incorporate the massive global efforts in understanding, diagnosing, and treating trauma induced coagulopathy. The evolving use of blood products as well as recently introduced hemostatic medications is reviewed in detail. The text provides therapeutic strategies to treat specific coagulation abnormalities following severe injury, which goes beyond the first edition that largely was based on describing the mechanisms causing coagulation abnormalities. Trauma Induced Coagulopathy 2nd Edition is a valuable reference to clinicians that are faced with specific clinical challenges when managing coagulopathy.