Insights into the Establishment of the Manila Clam on a Tidal Flat at the Southern End of an Introduced Range in Southern California,USA

Coastal ecosystem modifications have contributed to the spread of introduced species through alterations of historic disturbance regimes and resource availability, and increased propagule pressure. Frequency of occurrence of the Manila clam (Venerupis phillipinarum, Veneridae) in Southern California estuaries has increased from absent or sparse to common since the mid-1990s. Potential invasion vectors include seafood sales and aquaculture, and spread from established northern populations over decades. The clam’s post-settlement habitat preferences are, however, uncertain in this region. Our project aimed to identify factors associated with established patches of the clam within a bay toward the southern end of this introduced range. During summer 2013, we sampled 10 tidal flat sites in Mission Bay, San Diego; each containing an area with and without hard structure (e.g., riprap, boulders). We measured likely environmental influences (e.g., sediment variables, distance to ocean). Manila clam densities across the bay were most strongly associated with site, where highest densities were located in the northern and/or back halves of the bay; and weakly correlated with lower porewater salinities. Within sites, Manila clam density was enhanced in the presence of hard structure in most sites. Prevailing currents and salinity regimes likely contribute to bay wide distributions, while hard structures may provide suitable microhabitats (refuge from predators and physical stress) and larval entrapment within sites. Results provide insights into decisions about future shoreline management efforts. Finally, we identify directions for future study to better understand and therefore predict patterns of establishment of the Manila clam in the southern portion of its introduced range.     

Genetic Associations of Angiotensin-Converting Enzyme with Primary Intracerebral Hemorrhage: A Meta-analysis

Background

A number of studies have reported an association of angiotensin-converting enzyme (ACE) gene polymorphism with primary intracerebral hemorrhage (PICH), however the reports have demonstrated inconclusive results. To clarify this conflict, we updated the previously performed meta-analysis by Peck et al., which revealed negative results, by investigating the ACE polymorphism and its correlation to PICH.

Methods

PubMed and Embase databases (through Dec 2012) were searched for English articles on the relationship of the I/D polymorphism in ACE with PICH in humans. Summary odds ratios (ORs) were estimated and potential sources of heterogeneity and bias were explored.

Results

A total of 805 PICH cases and 1641 control cases obtained from 8 case-control studies were included. The results suggest that in dominant genetic models, the ACE I/D polymorphic variant was associated with a 58% increase in susceptibility risk of PICH (OR = 1.58; 95% CI = 1.07–2.35 for DD vs. DI+II). However, in the subgroup analysis based on race, a significant increased risk was found in Asian DD homozygote carriers (OR = 1.76 and 95% CI = 1.16–2.66 for DD vs. DI+II), but not in Caucasian DD homozygote carriers (OR = 1.18, 95% CI = 0.36–3.88, P = 0.784 for DD vs. DI+II). The heterogeneity between studies was remarkable, and its major sources of heterogeneity were due to the year in which the study was published. No potential publication bias was observed in dominant genetic models.

Conclusions

These data demonstrated evidence of a positive association between ACE I/D polymorphism with PICH, and suggested that the ACE gene is a PICH susceptible gene in Asian populations.     

Allosteric Regulation of DNA Cleavage and Sequence-Specificity through Run-On Oligomerization

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Invasion of tamarisk (<Emphasis Type="Italic">Tamarix</Emphasis> spp.) in a southern California salt marsh

Exotic plants have been demonstrated to be one of the greatest threats to wetlands, as they are capable of altering ecosystem-wide physical and biological properties. One of the most problematic invaders in the western United States has been salt cedar, Tamarix spp., and the impacts of this species in riparian and desert ecosystems have been well-documented. Here we document large populations of tamarisk in the intertidal salt marshes of Tijuana River National Estuarine Research Reserve, a habitat not often considered vulnerable to invasion by tamarisk. Initial research demonstrates that there are multiple species and hybrids of Tamarix invading the estuary and that the potential impact of tamarisk within this salt marsh is significant. This highlights the need for managers and scientists to be aware of the problems associated with tamarisk invasion of coastal marine habitats and to take early and aggressive action to combat any incipient invasion.     

A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation

Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators.     

Developing hybrid approaches to predict pKa values of ionizable groups

Accurate predictions of pKa values of titratable groups require taking into account all relevant processes associated with the ionization/deionization. Frequently, however, the ionization does not involve significant structural changes and the dominating effects are purely electrostatic in origin allowing accurate predictions to be made based on the electrostatic energy difference between ionized and neutral forms alone using a static structure and the subtle structural changes be accounted by using dielectric constant larger than two. On another hand, if the change of the charge state is accompanied by a large structural reorganization of the target protein, then the relevant conformational changes have to be explicitly taken into account in the pKa calculations. Here we report a hybrid approach that first predicts the titratable groups whose ionization is expected to cause large conformational changes, termed "problematic" residues, and then applies a special protocol on them, while the rest of the pK(a)s are predicted with rigid backbone approach as implemented in multi-conformation continuum electrostatics (MCCE) method. The backbone representative conformations for "problematic" groups are generated with either molecular dynamics simulations with charged and uncharged amino acid or with ab-initio local segment modeling. The corresponding ensembles are then used to calculate the titration curves of the "problematic" residues and then the results are averaged to obtain the corresponding pKa.     

Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal α7 nicotinic acetylcholine receptor

The pentameric acetylcholine‐binding protein (AChBP) is a soluble surrogate of the ligand binding domain of nicotinic acetylcholine receptors. Agonists bind within a nest of aromatic side chains contributed by loops C and F on opposing faces of each subunit interface. Crystal structures of Aplysia AChBP bound with the agonist anabaseine, two partial agonists selectively activating the α7 receptor, 3‐(2,4‐dimethoxybenzylidene)‐anabaseine and its 4‐hydroxy metabolite, and an indole‐containing partial agonist, tropisetron, were solved at 2.7–1.75 Å resolution. All structures identify the Trp 147 carbonyl oxygen as the hydrogen bond acceptor for the agonist‐protonated nitrogen. In the partial agonist complexes, the benzylidene and indole substituent positions, dictated by tight interactions with loop F, preclude loop C from adopting the closed conformation seen for full agonists. Fluctuation in loop C position and duality in ligand binding orientations suggest molecular bases for partial agonism at full‐length receptors. This study, while pointing to loop F as a major determinant of receptor subtype selectivity, also identifies a new template region for designing α7‐selective partial agonists to treat cognitive deficits in mental and neurodegenerative disorders.     

Virtual screening against acetylcholine binding protein

The nicotinic acetylcholine receptors (nAChRs) are a member of the ligand-gated ion channel family and play a key role in the transfer of information across neurological networks. The X-ray crystal structure of agonist-bound α(7) acetylcholine binding protein (AChBP) has been recognized as the most appropriate template to model the ligand-binding domain of nAChR for studying the molecular mechanism of the receptor-ligand interactions. Virtual screening of the National Cancer Institute diversity set, a library of 1990 compounds with nonredundant pharmacophore profiles, using AutoDock against AChBPs revealed 51 potential candidates. In vitro radioligand competition assays using [(3)H] epibatidine against the AChBPs from the freshwater snails, Lymnaea stagnalis, and from the marine species, Aplysia californica and the mutant (AcY55W), revealed seven compounds from the list of candidates that had micromolar to nanomolar affinities for the AChBPs. Further investigation on α(7)nAChR expressing in Xenopus oocytes and on the recombinant receptors with fluorescence resonance energy transfer (FRET)-based calcium sensor expressing in HEK cells showed that seven compounds were antagonists of α(7)nAChR, only one compound (NSC34352) demonstrated partial agonistic effect at low dose (10 μM), and two compounds (NSC36369 and NSC34352) were selective antagonists on α(7)nAchR with moderate potency. These hits serve as novel templates/scaffolds for development of more potent and specific in the AChR systems.     

P. falciparum enhances HIV replication in an experimental malaria challenge system

Co-infection with HIV and P. falciparum worsens the prognosis of both infections; however, the mechanisms driving this adverse interaction are not fully delineated. To evaluate this, we studied HIV-1 and P. falciparum interactions in vitro using peripheral blood mononuclear cells (PBMCs) from human malaria na?ve volunteers experimentally infected with P. falciparum in a malaria challenge trial. PBMCs collected before the malaria challenge and at several time points post-infection were infected with HIV-1 and co-cultured with either P. falciparum infected (iRBCs) or uninfected (uRBCs) red blood cells. HIV p24Ag and TNF-α, IFN-γ, IL-4, IL-6, IL-10, IL-17, and MIP-1α were quantified in the co-culture supernatants. In general, iRBCs stimulated more HIV p24Ag production by PBMCs than did uRBCs. HIV p24Ag production by PBMCs in the presence of iRBCs (but not uRBCs) further increased during convalescence (days 35, 56, and 90 post-challenge). In parallel, iRBCs induced higher secretion of pro-inflammatory cytokines (TNF-α, IFN-γ, and MIP-1α) than uRBCs, and production increased further during convalescence. Because the increase in p24Ag production occurred after parasitemia and generalized immune activation had resolved, our results suggest that enhanced HIV production is related to the development of anti-malaria immunity and may be mediated by pro-inflammatory cytokines.     

Testing the effects of an introduced palm on a riparian invertebrate community in southern california

Despite the iconic association of palms with semi-arid regions, most are introduced and can invade natural areas. Along the San Diego River (San Diego, California, USA), the introduced Canary Island date palm (Phoenix canariensis) forms dense patches among native riparian shrubs like arroyo willow (Salix lasiolepis). The structural differences between the palm and native shrubs are visually obvious, but little is known about palm's effects on the ecosystem. We tested for the effects of the palm on a riparian invertebrate community in June 2011 by comparing the faunal and environmental variables associated with palm and willow canopies, trunks and ground beneath each species. The palm invertebrate community had lower abundance and diversity, fewer taxa feeding on the host (e.g., specialized hemipterans), and more taxa likely using only the plant's physical structure (e.g., web-builders, oak moths, willow hemipterans). There were no observed effects on the ground-dwelling fauna. Faunal differences were due to the physical and trophic changes associated with palm presence, namely increased canopy density, unpalatable leaves, trunk rugosity, and litter accumulations. Palm presence and resulting community shifts may have further ecosystem-level effects through alteration of physical properties, food, and structural resources. These results were consistent with a recent study of invasive palm effects on desert spring arthropods, illustrating that effects may be relatively generalizable. Since spread of the palm is largely localized, but effects are dramatic where it does occur, we recommend combining our results with several further investigations in order to prioritize management decisions.