Helix termination and chain reversal: Crystal and molecular structure of the alpha,beta-dehydrooctapeptide Boc-Val Delta Phe-Phe-Ala-Leu-Ala-Delta Phe-Leu-OH

The crystal structure of the dehydro octapeptide Boc-Val-Delta Phe-Phe-Ala-Leu-Ala-Delta Phe-Leu-OH has been determined to atomic resolution by X-ray crystallographic methods. The crystals grown by slow evaporation of peptide solution in methanol/water are orthorhombic, space group P2(1)2(1)2(1). The unit cell parameters are a = 8.404(3), b = 25.598(2) and c = 27.946(3) Angstrom, Z = 4. The agreement factor is R = 7.58% for 3636 reflections having (\F-o\) greater than or equal to 3 sigma (\F-o\). The peptide molecule is characterised by a 3(10)-helix at the N-terminus and a pi-turn at the C-terminus. This conformation is exactly similar to the helix termination features observed in proteins. The pi-turn conformation observed in the octapeptide is in good agreement with the conformational features of pi-turns seen in some proteins. The alpha(L)-position in the pi-turn of the octapeptide is occupied by Delta Phe(7), which shows that even bulky residues can be accommodated in this position of the pi-turns. In proteins, it is generally seen that alpha(L)-position is occupied by glycine residue. No intermolecular head-to-tail hydrogen bonds are observed in solid state structure of the octapeptide. A water molecule located in the unit cell of the peptide molecule is mainly used to hold the peptide molecule together in the crystal. The conformation observed for the octapeptide might be useful to understand the helix termination and chain reversal in proteins and to construct helix terminators for denovo protein design.

Observation of Water-Mediated Helix-Terminating Conformation in a Dehydrophenylalanine Peptide: Crystal and Solution Structure of the Octapeptide Ac-.DELTA.Phe-Val-.DELTA.Phe-Phe-Ala-Val-.DELTA.Phe-Gly-OMe

We have synthesised and determined the solution conformation and X-ray crystal structure of the octapeptide Ac-Delta Phe(1)-Val(2)-Delta Phe(3)-Phe(4)-Ala(5)-Val(6)-Delta Phe(7)-Gly(8)-OCH3 (Delta Phe = alpha,beta-dehydrophenylalanine) containing three Delta Phe residues as conformation constraining residues. In the solid state, the peptide folds into (i) an N-terminal (3)10(R)-helical pentapeptide segment, (ii) a middle non-helical segment, and (iii) a C-terminal incipient (3)10(L)-helical segment. The results of H-1 NMR data also suggest that a similar multiple-turn conformation for the peptide is largely maintained in solution. Though the C-terminal helix is incipient, the overall conformation of the octapeptide matches well with the conformation of the hairpins reported. Comparison of the pi-turn seen in the octapeptide molecule with those observed in proteins at the C-terminal end of helixes shows the structural similarity among them. A water molecule mediates the 5 --> 2 hydrogen bond in the pi-turn region. This is the first example of a water-inserted pi-turn in oligopeptides reported so far. Comparison between the present octapeptide and another (3)10(R)-helical dehydro nonapeptide Boc-Val-Delta Phe-Phe-Ala-Phe-Delta Phe-Val-Delta Phe-Gly-OCH3 solved by us recently, demonstrates the possible sequence-dependent conformational variations in alpha,beta-dehydrophenylalanine-containing oligopeptides.

Role of two consecutive alpha,beta-dehydrophenylalanines in peptide structure: Crystal and molecular structure of Boc-Leu-Delta Phe-Delta Phe-Ala-Phe-NHMe

An N-alpha-protected model pentapeptide containing two consecutive Delta Phe residues, Boc-Leu-Delta Phe-Delta Phe-Ala-Phe-NHMe, has been synthesized by solution methods and fully characterized. H-1-nmr studies provided evidence for the occurrence of a significant population of a conformer having three consecutive, intramolecularly II-bonded beta-bends in solution. The solid state structure has been determined by x-ray diffraction methods. The crystals grown from aqueous methanol are orthorhombic, space group P2(1)2(1)2(1),, a = 11.503(2), b = 16.554(2), c = 22.107(3) Angstrom, V = 4209(1) Angstrom,(3) and Z = 4. The x-ray data were collected on a CAD4 diffractometer using CuKalpha radiation (lambda = 1.5418 Angstrom). The structure was determined using direct methods and refined by full-matrix least-squares procedure. The R factor is 5.3%. The molecule is characterized by a right handed 3(10)-helical conformation ((phi) = -68.2 degrees (psi) = -26.3 degrees), which is made up of two consecutive type III beta-bends and one type I beta-bend. In the solid state the helical molecules are aligned head-to-tail, thus forming long rod like structures. A comparison with other peptide structures containing consecutive Delta Phe residues is also provided. The present study confirms that the -Delta Phe-Delta Phe-sequence can be accommodated in helical structures. (C) 1997 John Wiley & Sons, Inc.

Number of prior episodes and the presence of depressive symptoms are associated with longer length of stay for patients with acute manic episodes

Background: Few studies have analyzed predictors of length of stay (LOS) in patients admitted due to acute bipolar manic episodes. The purpose of the present study was to estimate LOS and to determine the potential sociodemographic and clinical risk factors associated with a longer hospitalization. Such information could be useful to identify those patients at high risk for long LOS and to allocate them to special treatments, with the aim of optimizing their hospital management. Methods: This was a cross-sectional study recruiting adult patients with a diagnosis of bipolar disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria) who had been hospitalized due to an acute manic episode with a Young Mania Rating Scale total score greater than 20. Bivariate correlational and multiple linear regression analyses were performed to identify independent predictors of LOS. Results: A total of 235 patients from 44 centers were included in the study. The only factors that were significantly associated to LOS in the regression model were the number of previous episodes and the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at admission (P < 0.05). Conclusions: Patients with a high number of previous episodes and those with depressive symptoms during mania are more likely to stay longer in hospital. Patients with severe depressive symptoms may have a more severe or treatment-resistant course of the acute bipolar manic episode.

First Biennial Ocean Climate Summit: Finding Solutions for San Francisco Bay Area’s Coast and Ocean. Proceedings of the Summit: April 29, 2008, Golden Gate Club, The Presidio San Francisco, California

Executive Summary: The marine environment plays a critical role in the amount of carbon dioxide (CO2) that remains within Earth’s atmosphere, but has not received as much attention as the terrestrial environment when it comes to climate change discussions, programs, and plans for action. It is now apparent that the oceans have begun to reach a state of CO2 saturation, no longer maintaining the “steady-state” carbon cycle that existed prior to the Industrial Revolution. The increasing amount of CO2 present within the oceans and the atmosphere has an effect on climate and a cascading effect on the marine environment. Potential physical effects of climate change within the marine environment, including ocean acidification, changes in wind and upwelling regimes, increasing global sea surface temperatures, and sea level rise, can lead to dramatic, fundamental changes within marine and coastal ecosystems. Altered ecosystems can result in changing coastal economies through a reduction in marine ecosystem services such as commercial fish stocks and coastal tourism. Local impacts from climate change should be a front line issue for natural resource managers, but they often feel too overwhelmed by the magnitude of this issue to begin to take action. They may not feel they have the time, funding, or staff to take on a challenge as large as climate change and continue to not act as a result. Already, natural resource managers work to balance the needs of humans and the economy with ecosystem biodiversity and resilience. Responsible decisions are made each day that consider a wide variety of stakeholders, including community members, agencies, non-profit organizations, and business/industry. The issue of climate change must be approached as a collaborative effort, one that natural resource managers can facilitate by balancing human demands with healthy ecosystem function through research and monitoring, education and outreach, and policy reform. The Scientific Expert Group on Climate Change in their 2007 report titled, “Confronting Climate Change: Avoiding the Unmanageable and Managing the Unavoidable” charged governments around the world with developing strategies to “adapt to ongoing and future changes in climate change by integrating the implications of climate change into resource management and infrastructure development”. Resource managers must make future management decisions within an uncertain and changing climate based on both physical and biological ecosystem response to climate change and human perception of and response to the issue. Climate change is the biggest threat facing any protected area today and resource managers must lead the charge in addressing this threat. (PDF has 59 pages.)

Improving the biological activity of pyrrole-imidazole polyamides

DNA is nature’s blueprint, holding within it the genetic code that defines the structure and function of an organism. A complex network of DNA-binding proteins called transcription factors can largely control the flow of information from DNA, so modulating the function of transcription factors is a promising approach for treating many diseases. Pyrrole-imidazole (Py-Im) polyamides are a class of DNA-binding oligomers, which can be synthetically programmed to bind a target sequence of DNA. Due to their unique shape complementarity and a series of favorable hydrogen bonding interactions that occur upon DNA-binding, Py-Im polyamides can bind to the minor groove of DNA with affinities comparable to transcription factors. Previous studies have demonstrated that these cell-permeable small molecules can enter cell nuclei and disrupt the transcription factor-DNA interface, thereby repressing transcription. As the use of Py-Im polyamides has significant potential as a type of modular therapeutic platform, the need for polyamides with extremely favorable biological properties and high potency will be essential. Described herein, a variety of studies have been performed aimed at improving the biological activity of Py-Im polyamides. To improve the biological potency and cellular uptake of these compounds, we have developed a next-generation class of polyamides bearing aryl-turn moieties, a simple structural modification that allows significant improvements in cellular uptake. This strategy was also applied to a panel of high-affinity cyclic Py-Im polyamides, again demonstrating the remarkable effect minor structural changes can have on biological activity. The solubility properties of Py-Im polyamides and use of formulating reagents with their treatment have also been examined. Finally, we describe the study of Py-Im polyamides as a potential artificial transcription factor.

Part I. Influence of membrane morphology on ion-exchange and charge propagation in composite polyelectrolyte electrode coatings. Part II. Dynamic surface tension measurements of polarization relaxation at mercury pool electrodes by the method of Wilhelmy.

Part I. Novel composite polyelectrolyte materials were developed that exhibit desirable charge propagation and ion-retention properties. The morphology of electrode coatings cast from these materials was shown to be more important for its electrochemical behavior than its chemical composition.

Part II. The Wilhelmy plate technique for measuring dynamic surface tension was extended to electrified liquid-liquid interphases. The dynamical response of the aqueous NaF-mercury electrified interphase was examined by concomitant measurement of surface tension, current, and applied electrostatic potential. Observations of the surface tension response to linear sweep voltammetry and to step function perturbations in the applied electrostatic potential (e.g., chronotensiometry) provided strong evidence that relaxation processes proceed for time-periods that are at least an order of magnitude longer than the time periods necessary to establish diffusion equilibrium. The dynamical response of the surface tension is analyzed within the context of non-equilibrium thermodynamics and a kinetic model that requires three simultaneous first order processes.

Prediction of mesophotic coral distributions in the Au‘au Channel, Hawaii

The primary objective of this study was to predict the distribution of mesophotic hard corals in the Au‘au Channel in the Main Hawaiian Islands (MHI). Mesophotic hard corals are light-dependent corals adapted to the low light conditions at approximately 30 to 150 m in depth. Several physical factors potentially influence their spatial distribution, including aragonite saturation, alkalinity, pH, currents, water temperature, hard substrate availability and the availability of light at depth. Mesophotic corals and mesophotic coral ecosystems (MCEs) have increasingly been the subject of scientific study because they are being threatened by a growing number of anthropogenic stressors. They are the focus of this spatial modeling effort because the Hawaiian Islands Humpback Whale National Marine Sanctuary (HIHWNMS) is exploring the expansion of its scope—beyond the protection of the North Pacific Humpback Whale (Megaptera novaeangliae)—to include the conservation and management of these ecosystem components. The present study helps to address this need by examining the distribution of mesophotic corals in the Au‘au Channel region. This area is located between the islands of Maui, Lanai, Molokai and Kahoolawe, and includes parts of the Kealaikahiki, Alalākeiki and Kalohi Channels. It is unique, not only in terms of its geology, but also in terms of its physical oceanography and local weather patterns. Several physical conditions make it an ideal place for mesophotic hard corals, including consistently good water quality and clarity because it is flushed by tidal currents semi-diurnally; it has low amounts of rainfall and sediment run-off from the nearby land; and it is largely protected from seasonally strong wind and wave energy. Combined, these oceanographic and weather conditions create patches of comparatively warm, calm, clear waters that remain relatively stable through time. Freely available Maximum Entropy modeling software (MaxEnt 3.3.3e) was used to create four separate maps of predicted habitat suitability for: (1) all mesophotic hard corals combined, (2) Leptoseris, (3) Montipora and (4) Porites genera. MaxEnt works by analyzing the distribution of environmental variables where species are present, so it can find other areas that meet all of the same environmental constraints. Several steps (Figure 0.1) were required to produce and validate four ensemble predictive models (i.e., models with 10 replicates each). Approximately 2,000 georeferenced records containing information about mesophotic coral occurrence and 34 environmental predictors describing the seafloor’s depth, vertical structure, available light, surface temperature, currents and distance from shoreline at three spatial scales were used to train MaxEnt. Fifty percent of the 1,989 records were randomly chosen and set aside to assess each model replicate’s performance using Receiver Operating Characteristic (ROC), Area Under the Curve (AUC) values. An additional 1,646 records were also randomly chosen and set aside to independently assess the predictive accuracy of the four ensemble models. Suitability thresholds for these models (denoting where corals were predicted to be present/absent) were chosen by finding where the maximum number of correctly predicted presence and absence records intersected on each ROC curve. Permutation importance and jackknife analysis were used to quantify the contribution of each environmental variable to the four ensemble models.