A 22 year old right-handed man suffered a viral meningoencephalitis, possibly herpetic, resulting in bilateral damage to the temporal lobes as confirmed by appropriate clinical, electrophysiological and neuroradiological studies. Extended clinical neuropsychological evaluation documented all the characteristic features of the syndrome described by Klüver and Bucy following bilateral ablation of the temporal lobes in adult Rhesus monkeys, including "psychic blindness," oral exploration, hypermetamorphic impulse to action," lack of emotional responsiveness, aberrant sexual behavior, and an insatiable appetite. Additionally, a severe Wernicke's aphasia and a profound memory disorder were evident. The significance of these features as regards limbic function in the human is discussed.

Respiratory failure, driven by airways mucus obstruction, chronic inflammation and bacterial infections, is the main cause of mortality and morbidity in people with cystic fibrosis (CF) due to defects in the Cl- and HCO3− transport activity of the CF Transmembrane conductance Regulator (CFTR). Most recent pre-clinical and clinical studies have focused on restoring CFTR function by enhancing its trafficking or transport activity and show promising results. However, there are a significant number of patients that will not benefit from these CFTR-targeted therapies and it is therefore important to identify new non-CFTR targets that will restore lung function, by-passing CFTR dysfunction. The H+/K+-ATPase, ATP12A, has recently been identified as a potential novel target for CF therapies, since its acute inhibition by ouabain was shown to help restore mucus viscosity, mucociliary transport, and antimicrobial activity using in vitro CF airway models, and this effect was linked to an increase in the pH of the airway surface liquid (ASL). Here, we have evaluated the potential therapeutic use of ouabain by investigating the effect of chronically treating fully differentiated CF primary human airway epithelial cells (hAECs) with ouabain, under thin film conditions, resembling the in vivo situation. Our results show that although chronic treatment increased ASL pH, this correlated with a deleterious effect on epithelial integrity as assessed by LDH release, transepithelial electrical resistance, fluorescein flux, and ion transport. Since ATP12A shares approximately 65% identity with the gastric H+/K+-ATPase (ATP4A), we investigated the potential of using clinically approved ATP4A proton pump inhibitors (PPIs) for their ability to restore ASL pH in CF hAECs. We show that, despite not expressing ATP4A transcripts, acute exposure to the PPI esomeprezole, produced changes in intracellular pH that were consistent with the inhibition of H+ secretion, but this response was independent of ATP12A. More importantly, chronic exposure of CF hAECs to esomeprazole alkalinized the ASL without disrupting the epithelial barrier integrity, but this increase in ASL pH was consistent with a decrease in mRNA expression of ATP12A. We conclude that PPIs may offer a new approach to restore ASL pH in CF airways, which is independent of CFTR.

Plant cell walls are extracellular matrices that surround plant cells and critically influence basic cellular processes, such as cell division and expansion. Cellulose is a major constituent of plant cell walls, and this paracrystalline polysaccharide is synthesized at the plasma membrane by a large protein complex known as the cellulose synthase complex (CSC). Recent efforts have identified numerous protein components of the CSC, but relatively little is known about regulation of cellulose biosynthesis. Numerous phosphoproteomic surveys have identified phosphorylation events in CSC associated proteins, suggesting that protein phosphorylation may represent an important regulatory control of CSC activity. In this review, we discuss the composition and dynamics of the CSC in vivo, the catalog of CSC phosphorylation sites that have been identified, the function of experimentally examined phosphorylation events, and potential kinases responsible for these phosphorylation events. Additionally, we discuss future directions in cellulose synthase kinase identification and functional analyses of CSC phosphorylation sites.

The phosphoinositide, phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P), is a key signaling lipid in the inner leaflet of the cell plasma membrane, regulating diverse signaling pathways including cell growth and migration. In this study we investigate the impact of the hydrogen-bond donor lipids phosphatidylethanolamine (PE) and phosphatidylinositol (PI) on the charge and phase behavior of PI(3,4,5)P. PE and PI can interact with PI(3,4,5)P through hydrogen-bond formation, leading to altered ionization behavior and charge distribution within the PI(3,4,5)P headgroup. We quantify the altered PI(3,4,5)P ionization behavior using a multistate ionization model to obtain micro-pK values for the ionization of each phosphate group. The presence of PE leads to a decrease in the pK values for the initial deprotonation of PI(3,4,5)P, which describes the removal of the first proton of the three protons remaining at the phosphomonoester groups at pH 4.0. The decrease in these micro-pK values thus leads to a higher charge at low pH. Additionally, the charge distribution changes lead to increased charge on the 3- and 5-phosphates. In the presence of PI, the final deprotonation of PI(3,4,5)P is delayed, leading to a lower charge at high pH. This is due to a combination of hydrogen-bond formation between PI and PI(3,4,5)P, and increased surface charge due to the addition of the negatively charged PI. The interaction between PI and PI(3,4,5)P leads to the formation of PI and PI(3,4,5)P-enriched domains within the membrane. These domains may have a critical impact on PI(3,4,5)P-signaling. We also reevaluate results for all phosphatidylinositol bisphosphates as well as for PI(4,5)P in complex lipid mixtures with the multistate ionization model.

This is a commentary on educating leaders within the constraints of a highly technical curriculum. The U.S. Naval Academy's mission is to produce leaders for the nation. Many things compete for the time and attention of Midshipmen (the Academy's students). Greater attention must be paid to interpersonal communications skills in the formal and informal curriculum.

This study compares outdoor adventure-based leader development programs with a traditional non-outdoor program to test predictions about differential effects on leader development outcomes. Participants were drawn from the population of U.S. Naval Academy midshipmen involved in experiential leader development programs as a component of their training and education. Three concurrent experiential leader development programs were compared in terms of their impact on leader development outcomes, including leader identity, leader efficacy, and organizational cynicism. Two programs were outdoor, adventure-based experiences; one was a conventional, non-outdoor experience. We found that outdoor adventure-based programs varied in their effects on leader development outcomes, whereas the non-outdoor program had no significant effects on outcomes. Implications of these varied effects on leader development are discussed in terms of the implementation of theory-driven leadership development experiences.

Successful clinical implementation of gene delivery relies on the use of viral or nonviral based vectors to package and protect the therapeutic nucleic acid. These vehicles must also be able to direct the fate of the cargo once it has entered the cell to ensure that the nucleic acid is functional, and the desired outcome is achieved. Compared to viral vectors, non-viral vectors have the advantage of incorporating different material types such as lipids, polymers, and peptides to tune overall safety and efficacy. Peptides are especially powerful when used in gene delivery vectors as they are able to increase gene delivery efficacy by introducing new biochemical functionality. This review will discuss the use of peptides as central design components in non-viral gene delivery vectors. The contribution of the peptide component to the overall functionality of the delivery vehicle will be highlighted, with a focus on peptides as the only vehicle component or peptides in complex assemblies with lipids or polymers.

With recent improvements in both experimental and computational techniques it is now possible to gain insight into increasingly complex biomembrane systems. Combination of experiments and modelling has revealed the presence of ''islands'' of dimensions~0.5 mm formed by the aggregation of outer membrane proteins in bacteria. This phenomenon has an essential role in the turnover of proteins at the surface of Gram negative bacteria [1]. Nevertheless, at the frontier between these two fields lies a twilight zone which we can refer to as the mesoscale. This zone ranges from a few hundreds of nanometres to micrometres in size and from microseconds to millisecond in time. Despite increased efforts to cover this zone, it remains difficult to compare models and experimental observations, in part due to the limited scale of the simulations performed.Here, we present extensive work based on very large membrane models to better decipher the formation of clusters of membrane proteins at the mesoscale. Coarse grain molecular dynamics simulations of c.a. 120 nm2 systems were used to bridge the gap between modelling and experiments. We performed these simulations in different conditions of temperature and crowding to assess the dynamical properties of the proteins as well as the lipids in these systems. The simulations were then used to emulate fluorescence microscopy data in order to apply dedicated program to directly compare our models with results from supported membrane experiments. These results provide insights that can be extended to other crowded membrane protein systems.