Mechanism of subunit interaction at ketosynthase-dehydratase junctions in trans-AT polyketide synthases

Modular polyketide synthases (PKSs) produce numerous structurally complex natural products with diverse applications in medicine and agriculture. They typically consist of several multienzyme subunits that utilize structurally-defined docking domains (DDs) at their N- and C-termini to ensure correct assembly into functional multi-protein complexes. Here we report a fundamentally different mechanism for subunit assembly in trans-AT modular PKSs at the junction between ketosynthase (KS) and dehydratase (DH) domains. This involves direct interaction of a largely unstructured docking domain (DD) at the C-terminus of the KS with the surface of the downstream DH. Acyl transfer assays and mechanism-based cross-linking established that the DD is required for the KS to communicate with the acyl carrier protein appended to the DH. Two distinct regions for binding of the DD to the DH were identified using NMR spectroscopy, carbene foot-printing and mutagenesis, providing a foundation for future elucidation of the molecular basis for interaction specificity

A super-Earth transiting a nearby low-mass star

A decade ago, the detection of the first transiting extrasolar planet provided a direct constraint on its composition and opened the door to spectroscopic investigations of extrasolar planetary atmospheres. As such characterization studies are feasible only for transiting systems that are both nearby and for which the planet-to-star radius ratio is relatively large, nearby small stars have been surveyed intensively. Doppler studies and microlensing have uncovered a population of planets with minimum masses of 1.9-10 times the Earth's mass (M_Earth), called super-Earths. The first constraint on the bulk composition of this novel class of planets was afforded by CoRoT-7b, but the distance and size of its star preclude atmospheric studies in the foreseeable future. Here we report observations of the transiting planet GJ 1214b, which has a mass of 6.55 M_Earth and a radius 2.68 times Earth's radius (R_Earth), indicating that it is intermediate in stature between Earth and the ice giants of the Solar System. We find that the planetary mass and radius are consistent with a composition of primarily water enshrouded by a hydrogen-helium envelope that is only 0.05% of the mass of the planet. The atmosphere is probably escaping hydrodynamically, indicating that it has undergone significant evolution during its history. As the star is small and only 13 parsecs away, the planetary atmosphere is amenable to study with current observatories.Comment: 13 pages, 3 figures, published in Natur

Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS

Background: Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline’s functions are not well defined. Methods: Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy (1H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied. Results: Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14loCD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/ macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/ Cr (neuronal injury) and circulating CD14+CD16+ and CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation. Conclusion: Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation. Citation: Campbell JH, Burdo TH, Autissier P, Bombardier JP, Westmoreland SV, et al. (2011) Minocycline Inhibition of Monocyte Activation Correlate

Endophyte Microbiome Diversity in Micropropagated Atriplex canescens and Atriplex torreyi var griffithsii

Microbial diversity associated with micropropagated Atriplex species was assessed using microscopy, isolate culturing, and sequencing. Light, electron, and confocal microscopy revealed microbial cells in aseptically regenerated leaves and roots. Clone libraries and tag-encoded FLX amplicon pyrosequencing (TEFAP) analysis amplified sequences from callus homologous to diverse fungal and bacterial taxa. Culturing isolated some seed borne endophyte taxa which could be readily propagated apart from the host. Microbial cells were observed within biofilm-like residues associated with plant cell surfaces and intercellular spaces. Various universal primers amplified both plant and microbial sequences, with different primers revealing different patterns of fungal diversity. Bacterial and fungal TEFAP followed by alignment with sequences from curated databases revealed 7 bacterial and 17 ascomycete taxa in A. canescens, and 5 bacterial taxa in A. torreyi. Additional diversity was observed among isolates and clone libraries. Micropropagated Atriplex retains a complex, intimately associated microbiome which includes diverse strains well poised to interact in manners that influence host physiology. Microbiome analysis was facilitated by high throughput sequencing methods, but primer biases continue to limit recovery of diverse sequences from even moderately complex communities

Relationships among nutrient enrichment, detritus quality and quantity, and large-bodied shredding insect community structure

This is a post-peer-review, pre-copyedit version of an article published in Hydrobiologia. The final authenticated version is available online at: https://doi.org/10.1007/s10750-015-2208-2Anthropogenic nutrient enrichment of forested headwater streams can enhance detrital quality, decrease standing stocks, and alter the community structure of detrivorous insects, reducing nutrient retention and decreasing ecosystem functioning. Our objective was to determine if stoichiometric principles could be used to predict genus-specific shifts in shredding insect abundance and biomass across a dissolved nutrient and detritus food quality/quantity gradient. Detritus, insect, and water samples were collected from 12 Ozark Highland headwater streams. Significant correlations were found between stream nutrients and detrital quality but not quantity. Abundance and biomass responses of four out of five tested genera were accurately predicted by consumerresource stoichiometric theory. Low carbon:phosphorus (C:P) shredders responded positively to increased total phosphorus and/or food quality, and high C:P shredders exhibited neutral or negative responses to these variables. Genus-specific declines were correlated with decreased overall biomass in shredder assemblages, potentially causing disruptions in nutrient flows to higher level consumers with nutrient enrichment. This work provides further evidence that elevated nutrients may negatively impact shredding insect communities by altering the stoichiometry of detritus–detritivore interactions. A better understanding of stoichiometric mechanisms altering macroinvertebrate populations is needed to help inform water quality criteria for the management of headwater streams

Bridging taxonomic and disciplinary divides in infectious disease

Citation: Borer, E.T., & Antonovics, J. (2011). Bridging Taxonomic and Disciplinary Divides in Infectious Disease. EcoHealth 8, 261–267. https://doi.org/10.1007/s10393-011-0718-6Pathogens traverse disciplinary and taxonomic boundaries, yet infectious disease research occurs in many separate disciplines including plant pathology, veterinary and human medicine, and ecological and evolutionary sciences. These disciplines have different traditions, goals, and terminology, creating gaps in communication. Bridging these disciplinary and taxonomic gaps promises novel insights and important synergistic advances in control of infectious disease. An approach integrated across the plant-animal divide would advance our understanding of disease by quantifying critical processes including transmission, community interactions, pathogen evolution, and complexity at multiple spatial and temporal scales. These advances require more substantial investment in basic disease research