Solution conformation of Lewis a-derived selectin ligands is unaffected by anionic substituents at the 3'- and 6'- positions

The selectins are a family of proteins that mediate leukocytetethering and rolling along the vascular endothelium. E-, P-,and L-selectin recognize various derivatives of the Lewis^a andLewis^x trisaccharides. The distribution of negative chargeson the Lewis^a and Lewis^x oligosaccharides appears to be an importantfactor in their binding by the selectins. Previous work exploringthis electrostatic dependence found that a series of syntheticanionic trisaccharides, 3'-sulfo, 3'-phospho, 6'-sulfo, and3',6'-disulfo Lewis^a. (Glc), exhibited differing selectin inhibitoryefficacies. To explore the possibility that these differencesarise from conformational differences between the sugars, thesolution structures of these trisaccharides were determinedusing NMR and molecular dynamics simulations. Interproton distancesand interglycosidic torsion angles were determined at 37°Cusing NOESY buildup curves and 1D LRJ experiments, respectively.Data from both experiments agreed well with predictions madefrom 2000 picosecond unrestrained molecular dynamics simulations.We found that 3'-sulfation did not alter the core Lewis^a conformation,a finding that reaffirms the results of previous study. In addition,we found that sulfation at the 6' position also leaves the trisaccharideconformation unperturbed. This is significant because the proximityof the 6'-sulfate group to the fucose ring might have alteredthe canonical Lewis^a structure. The disulfate exhibited greaterflexibility than the other derivatives in dynamics simulations,but not so much as to affect NOE and heteronuclear couplingconstant measurements. Taken together, our findings supportthe use of Lewis^a as a template onto which charged groups maybe added without significantly altering the trisaccharide'sstructure. oligosaccharides molecular dynamics simulations NMR sulfated Lewis^a phosphorylated Lewis^a     

An examination of the epiphytic nature of Gambierdiscus toxicus, a dinoflagellate involved in ciguatera fish poisoning

Twenty-four specimen of macroalgae were collected in nearshore waters of the island of Hawaii, identified, and maintained to examine how the epiphytic relationship between Gambierdiscus toxicus (isolate BIG12) varied among the macroalgal species. Gambierdiscus cells were introduced to Petri dishes containing 100 g samples of each macroalgal host, which were examined at two, 16, 24, and every 24–72 h thereafter, over a 29-day period. Gambierdiscus proliferated in the presence of some host species (e.g., Galaxaura marginata and Jania sp.), but grew little in the presence of other species (e.g., Portieria hornemannii). Gambierdiscus exhibited high survival rates (>99%) in the presence of Chaetomorpha sp., but died before the end of the experiment (after 21 days) with other host species (e.g., Dictyota and Microdictyon spp.). Gambierdiscus avoided contact with P. hornemannii, but averaged up to 30% attachment with other host species. The numbers of Gambierdiscus cells belonging to one of three classes (alive and attached; alive and unattached; and dead) were determined for each time point. The 24 algal hosts were grouped according to their commonalities relative to these three classes using a Bray-Curtis similarity index, similarity profile (SIMPROF) permutation tests, and Multi-Dimensional Scaling (MDS) analysis (PRIMER 6). The resultant six groupings were used to construct different Gambierdiscus growth profiles for the different algal hosts. Group A is characterized by a preponderance of unattached cells and high mortality rates. Groups B, C, E, and F also displayed high proportions of unattached cells, but mortality either occurred later (Groups B and C) or rates were lower (Groups E and F). Group D had the highest proportion of attached cells. Group E contained three out of the four chlorophyte species, while Group F contained the majority of the rhodophytes. Over 50% of the species in Group F are considered to be palatable, whereas Groups A, B, and C are composed of species that exhibit chemical defenses against herbivory. The results of this study coupled with previous findings indicate that Gambierdiscus is not an obligate epiphyte; it can be free-swimming and found in the plankton. The conditions that lead to changes between epiphytic and planktonic stages need to be better studied in order to determine how they affect Gambierdiscus growth and physiology, connectivity and dispersion mechanisms, and toxin movement up into the foodweb.     

cGMP/Protein Kinase G Signaling Suppresses Inositol 1,4,5-Trisphosphate Receptor Phosphorylation and Promotes Endoplasmic Reticulum Stress in Photoreceptors of Cyclic Nucleotide-gated Channel-deficient Mice

Photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in phototransduction. Mutations in the cone CNG channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophies. We have shown endoplasmic reticulum (ER) stress-associated apoptotic cone death and increased phosphorylation of the ER Ca²⁺ channel inositol 1,4,5-trisphosphate receptor 1 (IP₃R1) in CNG channel-deficient mice. We also presented a remarkable elevation of cGMP and an increased activity of the cGMP-dependent protein kinase (protein kinase G, PKG) in CNG channel deficiency. This work investigated whether cGMP/PKG signaling regulates ER stress and IP₃R1 phosphorylation in CNG channel-deficient cones. Treatment with PKG inhibitor and deletion of guanylate cyclase-1 (GC1), the enzyme producing cGMP in cones, were used to suppress cGMP/PKG signaling in cone-dominant Cnga3^−/−/Nrl^−/− mice. We found that treatment with PKG inhibitor or deletion of GC1 effectively reduced apoptotic cone death, increased expression levels of cone proteins, and decreased activation of Müller glial cells. Furthermore, we observed significantly increased phosphorylation of IP₃R1 and reduced ER stress. Our findings demonstrate a role of cGMP/PKG signaling in ER stress and ER Ca²⁺ channel regulation and provide insights into the mechanism of cone degeneration in CNG channel deficiency.     

Participation and Contribution in Crowdsourced Surveys

This paper identifies trends within and relationships between the amount of participation and the quality of contributions in three crowdsourced surveys. Participants were asked to perform a collective problem solving task that lacked any explicit incentive: they were instructed not only to respond to survey questions but also to pose new questions that they thought might-if responded to by others-predict an outcome variable of interest to them. While the three surveys had very different outcome variables, target audiences, methods of advertisement, and lengths of deployment, we found very similar patterns of collective behavior. In particular, we found that: the rate at which participants submitted new survey questions followed a heavy-tailed distribution; the distribution in the types of questions posed was similar; and many users posed non-obvious yet predictive questions. By analyzing responses to questions that contained a built-in range of valid response we found that less than 0.2% of responses lay outside of those ranges, indicating that most participants tend to respond honestly to surveys of this form, even without explicit incentives for honesty. While we did not find a significant relationship between the quantity of participation and the quality of contribution for both response submissions and question submissions, we did find several other more nuanced participant behavior patterns, which did correlate with contribution in one of the three surveys. We conclude that there exists an optimal time for users to pose questions early on in their participation, but only after they have submitted a few responses to other questions. This suggests that future crowdsourced surveys may attract more predictive questions by prompting users to pose new questions at specific times during their participation and limiting question submission at non-optimal times.     

Optimal Mating Strategies for Preferentially Outcrossing Simultaneous Hermaphrodites in the Presence of Predators

The optimal timing for initiating reproduction (i.e., the age at first reproduction) is a critical life history trait describing aspects of an individual’s resource-allocation strategy. Recent theoretical and empirical work has demonstrated that this trait is also tied to mating system expression when individuals have the opportunity to reproduce via both self-fertilization and cross-fertilization. A strategy of “delayed selfing” has emerged as a “best of both worlds” arrangement where, in the absence of a mate, an individual will delay reproduction (selfing) to “wait” for a mate. Herein, we extend previously developed predictive optimization models for the timing of reproduction to a situation where organisms can allocate their resources to size-dependent and size-independent defensive strategies to counter the threat of predation. By incorporating inducible defenses into a predictive framework for analyzing life history expression and evolution, we can more accurately evaluate the role that allocation strategy plays in altering the optimal waiting time. We compare our model to previous models and empirical results highlighting that incorporation of inducible defenses into the model broadens the parameter space in which a waiting time is expected and often leads to a predicted waiting time that is longer than in the situation without inducible defenses. In particular, a waiting time is predicted to exist regardless of the strength of inbreeding depression in the population.     

Pathways of soil genesis in the Coast Range of Oregon, USA

Background and Aims

Soil chronosequences on marine terraces along the Pacific Coast of California and Oregon show evidence of podzolization, though soils ultimately evolve to Ultisols. It is not clear if this pathway of soil evolution can be extended to the humid, inland Oregon Coast Range.

Methods

We analyzed soil properties for a fluvial terrace chronosequence sampled along the Siuslaw River (Oregon, USA) about 50 km from the Pacific coast. The seven terraces ranged in age from <3.5 ky to nearly 1,000 ky.

Results

There was no evidence of early podsolization. Instead, evidence was found that andisolization starts early and occurs even in older soils when pedogenic iron accumulation and clay synthesis and illuviation dominate. Soils develop the morphology characteristic of Ultisols sometime between 20 and 70 ky, but high levels of oxalate extractable iron and aluminum satisfy criteria of an andic subgroup. Alfisols are not formed as an intermediary stage.

Conclusions

The lack of Spodosols inland is due to the inland shift from udic to ustic or xeric moisture regime, which favors summer drying and ripening of short-range order minerals rather than deep leaching or translocation. Other factors are higher pH, different organic chemistry and faster calcium cycling under the Douglas fir inland when compared to the Sitka spruce of the coastal terraces.     

Free energy transduction in a chemical motor model

Motor enzymes catalyse chemical reactions, like the hydrolysis of ATP, and in the process they also perform work. Recent studies indicate that motor enzymes perform work with specific biochemical steps in their catalysed reactions, challenging the classical view that work can only be performed within a biochemical state. To address these studies an alternative class of models, often referred to as chemical motor models, has emerged in which motors perform work with biochemical transitions. In this paper, I develop a novel, self-consistent framework for chemical motor models, which accommodates multiple pathways for free energy transfer, predicts rich behaviors from the simplest multi-motor systems, and provides important new insights into muscle and motor function.