Library Design in Combinatorial Chemistry by Monte Carlo Methods

Strategies for searching the space of variables in combinatorial chemistry experiments are presented, and a random energy model of combinatorial chemistry experiments is introduced. The search strategies, derived by analogy with the computer modeling technique of Monte Carlo, effectively search the variable space even in combinatorial chemistry experiments of modest size. Efficient implementations of the library design and redesign strategies are feasible with current experimental capabilities.Comment: 5 pages, 3 figure

Norspermidine is not a self-produced trigger for biofilm disassembly

SummaryFormation of Bacillus subtilis biofilms, consisting of cells encapsulated within an extracellular matrix of exopolysaccharide and protein, requires the polyamine spermidine. A recent study reported that (1) related polyamine norspermidine is synthesized by B. subtilis using the equivalent of the Vibrio cholerae biosynthetic pathway, (2) exogenous norspermidine at 25 μM prevents B. subtilis biofilm formation, (3) endogenous norspermidine is present in biofilms at 50–80 μM, and (4) norspermidine prevents biofilm formation by condensing biofilm exopolysaccharide. In contrast, we find that, at concentrations up to 200 μM, exogenous norspermidine promotes biofilm formation. We find that norspermidine is absent in wild-type B. subtilis biofilms at all stages, and higher concentrations of exogenous norspermidine eventually inhibit planktonic growth and biofilm formation in an exopolysaccharide-independent manner. Moreover, orthologs of the V. cholerae norspermidine biosynthetic pathway are absent from B. subtilis, confirming that norspermidine is not physiologically relevant to biofilm function in this species

Discovery of a black smoker vent field and vent fauna at the Arctic Mid-Ocean Ridge

The Arctic Mid-Ocean Ridge (AMOR) represents one of the most slow-spreading ridge systems on Earth. Previous attempts to locate hydrothermal vent fields and unravel the nature of venting, as well as the provenance of vent fauna at this northern and insular termination of the global ridge system, have been unsuccessful. Here, we report the first discovery of a black smoker vent field at the AMOR. The field is located on the crest of an axial volcanic ridge (AVR) and is associated with an unusually large hydrothermal deposit, which documents that extensive venting and long-lived hydrothermal systems exist at ultraslow-spreading ridges, despite their strongly reduced volcanic activity. The vent field hosts a distinct vent fauna that differs from the fauna to the south along the Mid-Atlantic Ridge. The novel vent fauna seems to have developed by local specialization and by migration of fauna from cold seeps and the Pacific

Mainstreaming marine biodiversity into the SDGs: The role of other effective area-based conservation measures (SDG 14.5)

This article explores the concept of “other effective area-based conservation measures” (OECMs) in the context of the UN Convention on Biological Diversity (CBD) Aichi Biodiversity Target 11 on marine protected areas and OECMs and its linkages to the Sustainable Development Goals (SDGs). It argues that mainstreaming biodiversity through CBD Aichi Biodiversity Targets’ implementation into the SDGs can contribute to a more systemic and comprehensive implementation of SDG 14.5 on conservation of at least 10% of marine and coastal areas. It argues that OECMs can complement MPAs and contribute to ecologically representative and effectively managed marine protected areas systems integrated into broader governance systems such as marine spatial planning. Selected global and local sectoral conservation measures are therefore highlighted in this analysis as potential forms of OECMs. At the local level, a case study of ecologically or biologically significant marine areas managed as locally managed marine areas (LMMAs) in Mozambique is discussed. This case study explores how multiple-use LMMAs, which respond to short-term fisher's needs and targeted biodiversity conservation, could contribute to the achievement of specific SDGs on food security, poverty elimination and resilient ecosystems if properly supported by long-term investments, strong institutions and integrated oceans management

Immunometabolic Signatures Predict Risk of Progression to Active Tuberculosis and Disease Outcome.

There remains a pressing need for biomarkers that can predict who will progress to active tuberculosis (TB) after exposure to Mycobacterium tuberculosis (MTB) bacterium. By analyzing cohorts of household contacts of TB index cases (HHCs) and a stringent non-human primate (NHP) challenge model, we evaluated whether integration of blood transcriptional profiling with serum metabolomic profiling can provide new understanding of disease processes and enable improved prediction of TB progression. Compared to either alone, the combined application of pre-existing transcriptome- and metabolome-based signatures more accurately predicted TB progression in the HHC cohorts and more accurately predicted disease severity in the NHPs. Pathway and data-driven correlation analyses of the integrated transcriptional and metabolomic datasets further identified novel immunometabolomic signatures significantly associated with TB progression in HHCs and NHPs, implicating cortisol, tryptophan, glutathione, and tRNA acylation networks. These results demonstrate the power of multi-omics analysis to provide new insights into complex disease processes

Adaptive and maladaptive consequences of “matching habitat choice:” lessons from a rapidly-evolving butterfly metapopulation

Relationships between biased dispersal and local adaptation are currently debated. Here, I show how prior work on wild butterflies casts a novel light on this topic. “Preference” is defined as the set of likelihoods of accepting particular resources after encountering them. So defined, butterfly oviposition preferences are heritable habitat adaptations distinct from both habitat preference and biased dispersal, but influencing both processes. When a butterfly emigrates after its oviposition preference begins to reduce realized fecundity, the resulting biased dispersal is analogous to that occurring when a fish emigrates after its morphological habitat adaptations reduce its feeding rate. I illustrate preference-biased dispersal with examples from metapopulations of Melitaea cinxia and Euphydryas editha. E. editha were feeding on a well-defended host, Pedicularis, when humans created patches in which Pedicularis was killed and a less-defended host, Collinsia, was rendered phenologically available. Patch-specific natural selection favoured oviposition on Collinsia in logged (“clearing”) patches and on Pedicularis in undisturbed open forest. Quantitative variation in post-alighting oviposition preference was heritable, and evolved to be consistently different between patch types. This difference was driven more by biased dispersal than by spatial variation of natural selection. Insects developing on Collinsia in clearings retained adaptations to Pedicularis in clutch size, geotaxis and oviposition preference, forcing them to choose between emigrating in search of forest habitats with Pedicularis or staying and failing to find their preferred host. Insects that stayed suffered reduction of realized fecundity after delayed oviposition on Collinsia. Those that emigrated suffered even greater fitness penalty from consistently low offspring survival on Pedicularis. Paradoxically, most emigrants reduced both their own fitness and that of the recipient populations by dispersing from a benign natal habitat to which they were maladapted into a more demanding habitat to which they were well-adapted. “Matching habitat choice” reduced fitness when evolutionary lag rendered traditional cues unreliable in a changing environment

Impacts of cultural dynamics on conservation of Suakin, Sudan

This article was published in the journal Proceedings of the ICE- Engineering Sustainability [http://www.icevirtuallibrary.com/content/serial/ensu]. Permission is granted by ICE Publishing to print one copy for personal use. Any other use of these PDF files is subject to reprint fees.The aim of this work was to explore the impact of local cultural dynamics on the conservation of the built heritage of Suakin, an abandoned historic port on the Red Sea coast of Sudan, through a collaborative stakeholder approach. Key representatives of local stakeholder groups attended a two-day workshop and took part in a series of collaborative activities. These encompassed the production of a rank-ordered list of the key local cultural dynamics impacting on the port's conservation, agreement to a number of actions to address obstacles to conservation, identification of local cultural values collectively determined by stakeholder and confirmation of the value of an integrated conservation approach. The workshop enabled a shared understanding and responsibility between stakeholders and established a commitment to further action to address the key local cultural dynamics impacting on the conservation. This collaborative stakeholder participation represented a new step in the port's conservation and invited the development of more formal protocols to enable the equal representation and participation of stakeholders in future conservation activities and initiatives

Identification of Lysine 37 of Histone H2B as a Novel Site of Methylation

Recent technological advancements have allowed for highly-sophisticated mass spectrometry-based studies of the histone code, which predicts that combinations of post-translational modifications (PTMs) on histone proteins result in defined biological outcomes mediated by effector proteins that recognize such marks. While significant progress has been made in the identification and characterization of histone PTMs, a full appreciation of the complexity of the histone code will require a complete understanding of all the modifications that putatively contribute to it. Here, using the top-down mass spectrometry approach for identifying PTMs on full-length histones, we report that lysine 37 of histone H2B is dimethylated in the budding yeast Saccharomyces cerevisiae. By generating a modification-specific antibody and yeast strains that harbor mutations in the putative site of methylation, we provide evidence that this mark exist in vivo. Importantly, we show that this lysine residue is highly conserved through evolution, and provide evidence that this methylation event also occurs in higher eukaryotes. By identifying a novel site of histone methylation, this study adds to our overall understanding of the complex number of histone modifications that contribute to chromatin function

Accelerated Evolution of the Prdm9 Speciation Gene across Diverse Metazoan Taxa

The onset of prezygotic and postzygotic barriers to gene flow between populations is a hallmark of speciation. One of the earliest postzygotic isolating barriers to arise between incipient species is the sterility of the heterogametic sex in interspecies' hybrids. Four genes that underlie hybrid sterility have been identified in animals: Odysseus, JYalpha, and Overdrive in Drosophila and Prdm9 (Meisetz) in mice. Mouse Prdm9 encodes a protein with a KRAB motif, a histone methyltransferase domain and several zinc fingers. The difference of a single zinc finger distinguishes Prdm9 alleles that cause hybrid sterility from those that do not. We find that concerted evolution and positive selection have rapidly altered the number and sequence of Prdm9 zinc fingers across 13 rodent genomes. The patterns of positive selection in Prdm9 zinc fingers imply that rapid evolution has acted on the interface between the Prdm9 protein and the DNA sequences to which it binds. Similar patterns are apparent for Prdm9 zinc fingers for diverse metazoans, including primates. Indeed, allelic variation at the DNA–binding positions of human PRDM9 zinc fingers show significant association with decreased risk of infertility. Prdm9 thus plays a role in determining male sterility both between species (mouse) and within species (human). The recurrent episodes of positive selection acting on Prdm9 suggest that the DNA sequences to which it binds must also be evolving rapidly. Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis. We propose a hypothetical model in which incompatibilities between Prdm9-binding specificity and satellite DNAs provide the molecular basis for Prdm9-mediated hybrid sterility. We suggest that Prdm9 should be investigated as a candidate gene in other instances of hybrid sterility in metazoans