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1.  In his Elements 
PMCID: PMC4173718
2.  Lost for Words 
PMCID: PMC4141588  PMID: 25179045
3.  The CBT Panacea 
PMCID: PMC4141603
4.  Resistant Microbial Cooccurrence Patterns Inferred by Network Topology 
Although complex cooccurrence patterns have been described for microbes in natural communities, these patterns have scarcely been interpreted in the context of ecosystem functioning and stability. Here we constructed networks from species cooccurrences between pairs of microorganisms which were extracted from five individual aquatic time series, including a dystrophic and a eutrophic lake as well as an open ocean site. The resulting networks exhibited higher clustering coefficients, shorter path lengths, and higher average node degrees and levels of betweenness than those of random networks. Moreover, simulations demonstrated that taxa with a large number of cooccurrences and placement at convergence positions in the network, so-called “hubs” and “bottlenecks,” confer resistance against random removal of “taxa.” Accordingly, we refer to cooccurrences at convergence positions as system-relevant interdependencies, as they, like hubs and bottlenecks, determine network topology. These topology features of the cooccurrence networks point toward microbial community dynamics being resistant over time and thus could provide indicators for the state of ecosystem stability.
PMCID: PMC4345367  PMID: 25576616
5.  Inferring Phytoplankton, Terrestrial Plant and Bacteria Bulk δ¹³C Values from Compound Specific Analyses of Lipids and Fatty Acids 
PLoS ONE  2015;10(7):e0133974.
Stable isotope mixing models in aquatic ecology require δ13C values for food web end members such as phytoplankton and bacteria, however it is rarely possible to measure these directly. Hence there is a critical need for improved methods for estimating the δ13C ratios of phytoplankton, bacteria and terrestrial detritus from within mixed seston. We determined the δ13C values of lipids, phospholipids and biomarker fatty acids and used these to calculate isotopic differences compared to the whole-cell δ13C values for eight phytoplankton classes, five bacterial taxa, and three types of terrestrial organic matter (two trees and one grass). The lipid content was higher amongst the phytoplankton (9.5±4.0%) than bacteria (7.3±0.8%) or terrestrial matter (3.9±1.7%). Our measurements revealed that the δ13C values of lipids followed phylogenetic classification among phytoplankton (78.2% of variance was explained by class), bacteria and terrestrial matter, and there was a strong correlation between the δ13C values of total lipids, phospholipids and individual fatty acids. Amongst the phytoplankton, the isotopic difference between biomarker fatty acids and bulk biomass averaged -10.7±1.1‰ for Chlorophyceae and Cyanophyceae, and -6.1±1.7‰ for Cryptophyceae, Chrysophyceae and Diatomophyceae. For heterotrophic bacteria and for type I and type II methane-oxidizing bacteria our results showed a -1.3±1.3‰, -8.0±4.4‰, and -3.4±1.4‰ δ13C difference, respectively, between biomarker fatty acids and bulk biomass. For terrestrial matter the isotopic difference averaged -6.6±1.2‰. Based on these results, the δ13C values of total lipids and biomarker fatty acids can be used to determine the δ13C values of bulk phytoplankton, bacteria or terrestrial matter with ± 1.4‰ uncertainty (i.e., the pooled SD of the isotopic difference for all samples). We conclude that when compound-specific stable isotope analyses become more widely available, the determination of δ13C values for selected biomarker fatty acids coupled with established isotopic differences, offers a promising way to determine taxa-specific bulk δ13C values for the phytoplankton, bacteria, and terrestrial detritus embedded within mixed seston.
PMCID: PMC4514774  PMID: 26208114
6.  Supporting and enhancing peer review in the BJGP 
The British Journal of General Practice  2014;64(624):e459-e461.
PMCID: PMC4073733  PMID: 24982500
7.  Television: The GP Will See You Now: GPs: Behind Closed Doors 
PMCID: PMC4073712  PMID: 24982479
8.  The Best of Times ... 
PMCID: PMC4001136  PMID: 24771807
9.  Making research matter 
PMCID: PMC4001156  PMID: 24771808
10.  How The Light Gets In 
PMCID: PMC4001164
11.  Structure-Function Analysis of STING Activation by c[G(2′,5′)pA(3′,5′)p] and Targeting by Antiviral DMXAA 
Cell  2013;154(4):748-762.
Binding of dsDNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) triggers formation of the metazoan second messenger c[G(2′,5′)pA(3′,5′)p], which binds the signaling protein STING with subsequent activation of the interferon (IFN) pathway. We show that human hSTINGH232 adopts a ‘‘closed’’ conformation upon binding c[G(2′,5′)pA(3′,5′)p] and its linkage isomer c[G(2′,5′)pA(2′,5′)p], as does mouse mStingR231 on binding c[G(2′,5′)pA(3′,5′)p], c[G(3′,5′)pA(3′,5′)p] and the antiviral agent DMXAA, leading to similar ‘‘closed’’ conformations. Comparing hSTING to mSting, 2′,5′-linkage-containing cGAMP isomers were more specific triggers of the IFN pathway compared to the all-3′,5′-linkage isomer. Guided by structural information, we identified a unique point mutation (S162A) placed within the cyclic-dinucleotide-binding site of hSTING that rendered it sensitive to the otherwise mouse-specific drug DMXAA, a conclusion validated by binding studies. Our structural and functional analysis highlights the unexpected versatility of STING in the recognition of natural and synthetic ligands within a small-molecule pocket created by the dimerization of STING.
PMCID: PMC4386733  PMID: 23910378
12.  Risky Business 
PMCID: PMC3964468  PMID: 24686861
13.  Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase 
Cell  2013;153(5):1094-1107.
Recent studies identified cyclic GMP-AMP (cGAMP) as a metazoan second messenger triggering an interferon response. cGAMP is generated from GTP and ATP by cytoplasmic dsDNA sensor cGAMP synthase (cGAS). We combined structural, chemical, biochemical, and cellular assays to demonstrate that this second messenger contains G(2′,5′)pA and A(3′,5′)pG phosphodiester linkages, designated c[G(2′,5′) pA(3′,5′)p]. We show that, upon dsDNA binding, cGAS is activated through conformational transitions, resulting in formation of a catalytically competent and accessible nucleotide-binding pocket for generation of c[G(2′,5′)pA(3′,5′)p]. We demonstrate that cyclization occurs in a stepwise manner through initial generation of 5′-pppG(2′,5′)pA prior to cyclization to c[G(2′,5′)pA(3′,5′)p], with the latter positioned precisely in the catalytic pocket. Mutants of cGAS dsDNA-binding or catalytic pocket residues exhibit reduced or abrogated activity. Our studies have identified c[G(2′,5′)pA(3′,5′)p] as a founding member of a family of metazoan 2′,5′-containing cyclic heterodinucleotide second messengers distinct from bacterial 3′,5′ cyclic dinucleotides.
PMCID: PMC4382009  PMID: 23647843
14.  Lake size and fish diversity determine resource use and trophic position of a top predator in high-latitude lakes 
Ecology and Evolution  2015;5(8):1664-1675.
Prey preference of top predators and energy flow across habitat boundaries are of fundamental importance for structure and function of aquatic and terrestrial ecosystems, as they may have strong effects on production, species diversity, and food-web stability. In lakes, littoral and pelagic food-web compartments are typically coupled and controlled by generalist fish top predators. However, the extent and determinants of such coupling remains a topical area of ecological research and is largely unknown in oligotrophic high-latitude lakes. We analyzed food-web structure and resource use by a generalist top predator, the Arctic charr Salvelinus alpinus (L.), in 17 oligotrophic subarctic lakes covering a marked gradient in size (0.5–1084 km2) and fish species richness (2–13 species). We expected top predators to shift from littoral to pelagic energy sources with increasing lake size, as the availability of pelagic prey resources and the competition for littoral prey are both likely to be higher in large lakes with multispecies fish communities. We also expected top predators to occupy a higher trophic position in lakes with greater fish species richness due to potential substitution of intermediate consumers (prey fish) and increased piscivory by top predators. Based on stable carbon and nitrogen isotope analyses, the mean reliance of Arctic charr on littoral energy sources showed a significant negative relationship with lake surface area, whereas the mean trophic position of Arctic charr, reflecting the lake food-chain length, increased with fish species richness. These results were supported by stomach contents data demonstrating a shift of Arctic charr from an invertebrate-dominated diet to piscivory on pelagic fish. Our study highlights that, because they determine the main energy source (littoral vs. pelagic) and the trophic position of generalist top predators, ecosystem size and fish diversity are particularly important factors influencing function and structure of food webs in high-latitude lakes.
PMCID: PMC4409414  PMID: 25937909
Benthic; energy mobilization; food-chain length; habitat coupling; lake morphometry; predation; resource competition; stable isotope analysis; trophic niche
15.  The Madness of the King 
PMCID: PMC3933830
16.  Editor’s Briefing 
PMCID: PMC3933856  PMID: 24567624
17.  Mapping Structurally Defined Guanine Oxidation Products along DNA Duplexes: Influence of Local Sequence Context and Endogenous Cytosine Methylation 
DNA oxidation by reactive oxygen species is nonrandom, potentially leading to accumulation of nucleobase damage and mutations at specific sites within the genome. We now present the first quantitative data for sequence-dependent formation of structurally defined oxidative nucleobase adducts along p53 gene-derived DNA duplexes using a novel isotope labeling-based approach. Our results reveal that local nucleobase sequence context differentially alters the yields of 2,2,4-triamino-2H-oxal-5-one (Z) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (OG) in double stranded DNA. While both lesions are overproduced within endogenously methylated MeCG dinucleotides and at 5′ Gs in runs of several guanines, the formation of Z (but not OG) is strongly preferred at solvent-exposed guanine nucleobases at duplex ends. Targeted oxidation of MeCG sequences may be caused by a lowered ionization potential of guanine bases paired with MeC and the preferential intercalation of riboflavin photosensitizer adjacent to MeC:G base pairs. Importantly, some of the most frequently oxidized positions coincide with the known p53 lung cancer mutational “hotspots” at codons 245 (GGC), 248 (CGG), and 158 (CGC) respectively, supporting a possible role of oxidative degradation of DNA in the initiation of lung cancer.
PMCID: PMC3985951  PMID: 24571128
18.  Synthesis of c-di-GMP Analogs with Thiourea, Urea, Carbodiimide, and Guanidinium Linkages 
Organic letters  2013;16(1):158-161.
The first syntheses of neutral thiourea, urea, and carbodiimide analogs, along with two guanidinium analogs, of the bacterial signaling molecule cyclic diguanosine monophosphate (c-di-GMP) are reported. The key intermediate, obtained in nine steps, is a 3′-amino-5′-azido-3′,5′-dideoxy derivative. The 5′-azide serves as a masked amine from which the amine is obtained by Staudinger reduction, while the 3′-amine is converted to an isothiocyanate that, while stable to chromatography, and Staudinger conditions, nevertheless reacts well with the 5′-amine.
PMCID: PMC3933394  PMID: 24313312
19.  Editor’s Briefing 
PMCID: PMC3876142  PMID: 24567548
20.  We’ve been Expecting You MR Boyd 
PMCID: PMC3876149
21.  Editor’s Briefing 
PMCID: PMC3839352
22.  Future Perfect 
PMCID: PMC4240112  PMID: 25452507
23.  Flesh and Bone Francis Bacon/Henry Moore 
PMCID: PMC3809417
24.  Your Tube 
PMCID: PMC4220237  PMID: 25348960
25.  Editor’s Briefing 
PMCID: PMC3782766

Results 1-25 (204)