Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming.

Predicting regulatory potential from primary DNA sequences or transcription factor binding patterns is not possible. However, the annotation of the genome by chromatin proteins, histone modifications, and differential compaction is largely sufficient to reveal the locations of genes and their differential activity states. The Polycomb Group (PcG) and Trithorax Group (TrxG) proteins are the central players in this cell type-specific chromatin organization. PcG function was originally viewed as being solely repressive and irreversible, as observed at the homeotic loci in flies and mammals. However, it is now clear that modular and reversible PcG function is essential at most developmental genes. Focusing mainly on recent advances, we review evidence for how PcG and TrxG patterns change dynamically during cell type transitions. The ability to implement cell type-specific transcriptional programming with exquisite fidelity is essential for normal development.

Epigenetic Regulation of Tick Biology and Vectorial Capacity.

Ticks exist across diverse environments and transmit numerous pathogens. Due to their long and unique life cycles, these arthropods likely evolved robust epigenetic mechanisms that provide sustainable responses and buffers against extreme environmental conditions. Herein, we highlight how the study of the epigenetic basis of tick biology and vectorial capacity will enrich our knowledge of tick-borne infections.

Genome-wide chromosomal association of Upf1 is linked to Pol II transcription in Schizosaccharomyces pombe.

Although the RNA helicase Upf1 has hitherto been examined mostly in relation to its cytoplasmic role in nonsense mediated mRNA decay (NMD), here we report high-throughput ChIP data indicating genome-wide association of Upf1 with active genes in Schizosaccharomyces pombe. This association is RNase sensitive, correlates with Pol II transcription and mRNA expression levels. Changes in Pol II occupancy were detected in a Upf1 deficient (upf1Δ) strain, prevalently at genes showing a high Upf1 relative to Pol II association in wild-type. Additionally, an increased Ser2 Pol II signal was detected at all highly transcribed genes examined by ChIP-qPCR. Furthermore, upf1Δ cells are hypersensitive to the transcription elongation inhibitor 6-azauracil. A significant proportion of the genes associated with Upf1 in wild-type conditions are also mis-regulated in upf1Δ. These data envisage that by operating on the nascent transcript, Upf1 might influence Pol II phosphorylation and transcription.

Integrated CO2 capture and electrochemical upgradation: the underpinning mechanism and techno-chemical analysis.

Coupling post-combustion CO2 capture with electrochemical utilization (CCU) is a quantum leap in renewable energy science since it eliminates the cost and energy involved in the transport and storage of CO2. However, the major challenges involved in industrial scale implementation are selecting an appropriate solvent/electrolyte for CO2 capture, modeling an appropriate infrastructure by coupling an electrolyser with a CO2 point source and a separator to isolate CO2 reduction reaction (CO2RR) products, and finally selection of an appropriate electrocatalyst. In this review, we highlight the major difficulties with detailed mechanistic interpretation in each step, to find out the underpinning mechanism involved in the integration of electrochemical CCU to achieve higher-value products. In the past decades, most of the studies dealt with individual parts of the integration process, i.e., either selecting a solvent for CO2 capture, designing an electrocatalyst, or choosing an ideal electrolyte. In this context, it is important to note that solvents such as monoethanolamine, bicarbonate, and ionic liquids are often used as electrolytes in CO2 capture media. Therefore, it is essential to fabricate a cost-effective electrolyser that should function as a reversible binder with CO2 and an electron pool capable of recovering the solvent to electrolyte reversibly. For example, reversible ionic liquids, which are non-ionic in their normal forms, but produce ionic forms after CO2 capture, can be further reverted back to their original non-ionic forms after CO2 release with almost 100% efficiency through the chemical or thermal modulations. This review also sheds light on a focused techno-economic evolution for converting the electrochemically integrated CCU process from a pilot-scale project to industrial-scale implementation. In brief, this review article will summarize a state-of-the-art argumentation of challenges and outcomes over the different segments involved in electrochemically integrated CCU to stimulate urgent progress in the field.

Epigenetic Regulation by Polycomb Complexes from Drosophila to Human and Its Relation to Communicable Disease Pathogenesis.

Although all cells in the human body are made of the same DNA, these cells undergo differentiation and behave differently during development, through integration of external and internal stimuli via 'specific mechanisms.' Epigenetics is one such mechanism that comprises DNA/RNA, histone modifications, and non-coding RNAs that regulate transcription without changing the genetic code. The discovery of the first Polycomb mutant phenotype in Drosophila started the study of epigenetics more than 80 years ago. Since then, a considerable number of Polycomb Group (PcG) genes in Drosophila have been discovered to be preserved in mammals, including humans. PcG proteins exert their influence through gene repression by acting in complexes, modifying histones, and compacting the chromatin within the nucleus. In this article, we discuss how our knowledge of the PcG repression mechanism in Drosophila translates to human communicable disease research.

Formation of a Polycomb-Domain in the Absence of Strong Polycomb Response Elements.

Polycomb group response elements (PREs) in Drosophila are DNA-elements that recruit Polycomb proteins (PcG) to chromatin and regulate gene expression. PREs are easily recognizable in the Drosophila genome as strong peaks of PcG-protein binding over discrete DNA fragments; many small but statistically significant PcG peaks are also observed in PcG domains. Surprisingly, in vivo deletion of the four characterized strong PREs from the PcG regulated invected-engrailed (inv-en) gene complex did not disrupt the formation of the H3K27me3 domain and did not affect inv-en expression in embryos or larvae suggesting the presence of redundant PcG recruitment mechanism. Further, the 3D-structure of the inv-en domain was only minimally altered by the deletion of the strong PREs. A reporter construct containing a 7.5kb en fragment that contains three weak peaks but no large PcG peaks forms an H3K27me3 domain and is PcG-regulated. Our data suggests a model for the recruitment of PcG-complexes to Drosophila genes via interactions with multiple, weak PREs spread throughout an H3K27me3 domain.

Combgap contributes to recruitment of Polycomb group proteins in Drosophila.

Polycomb group (PcG) proteins are responsible for maintaining the silenced transcriptional state of many developmentally regulated genes. PcG proteins are organized into multiprotein complexes that are recruited to DNA via cis-acting elements known as "Polycomb response elements" (PREs). In Drosophila, PREs consist of binding sites for many different DNA-binding proteins, some known and others unknown. Identification of these DNA-binding proteins is crucial to understanding the mechanism of PcG recruitment to PREs. We report here the identification of Combgap (Cg), a sequence-specific DNA-binding protein that is involved in recruitment of PcG proteins. Cg can bind directly to PREs via GTGT motifs and colocalizes with the PcG proteins Pleiohomeotic (Pho) and Polyhomeotic (Ph) at the majority of PREs in the genome. In addition, Cg colocalizes with Ph at a number of targets independent of Pho. Loss of Cg leads to decreased recruitment of Ph at only a subset of sites; some of these sites are binding sites for other Polycomb repressive complex 1 (PRC1) components, others are not. Our data suggest that Cg can recruit Ph in the absence of PRC1 and illustrate the diversity and redundancy of PcG protein recruitment mechanisms.

Comparing molecules and solids across structural and alchemical space.

Evaluating the (dis)similarity of crystalline, disordered and molecular compounds is a critical step in the development of algorithms to navigate automatically the configuration space of complex materials. For instance, a structural similarity metric is crucial for classifying structures, searching chemical space for better compounds and materials, and driving the next generation of machine-learning techniques for predicting the stability and properties of molecules and materials. In the last few years several strategies have been designed to compare atomic coordination environments. In particular, the smooth overlap of atomic positions (SOAPs) has emerged as an elegant framework to obtain translation, rotation and permutation-invariant descriptors of groups of atoms, underlying the development of various classes of machine-learned inter-atomic potentials. Here we discuss how one can combine such local descriptors using a regularized entropy match (REMatch) approach to describe the similarity of both whole molecular and bulk periodic structures, introducing powerful metrics that enable the navigation of alchemical and structural complexities within a unified framework. Furthermore, using this kernel and a ridge regression method we can predict atomization energies for a database of small organic molecules with a mean absolute error below 1 kcal mol(-1), reaching an important milestone in the application of machine-learning techniques for the evaluation of molecular properties.

Visualization of the joining of ribosomal subunits reveals the presence of 80S ribosomes in the nucleus.

In eukaryotes the 40S and 60S ribosomal subunits are assembled in the nucleolus, but there appear to be mechanisms preventing mRNA binding, 80S formation, and initiation of translation in the nucleus. To visualize association between ribosomal subunits, we tagged pairs of Drosophila ribosomal proteins (RPs) located in different subunits with mutually complementing halves of fluorescent proteins. Pairs of tagged RPs expected to interact, or be adjacent in the 80S structure, showed strong fluorescence, while pairs that were not in close proximity did not. Moreover, the complementation signal is found in ribosomal fractions and it was enhanced by translation elongation inhibitors and reduced by initiation inhibitors. Our technique achieved 80S visualization both in cultured cells and in fly tissues in vivo. Notably, while the main 80S signal was in the cytoplasm, clear signals were also seen in the nucleolus and at other nuclear sites. Furthermore, we detected rapid puromycin incorporation in the nucleolus and at transcription sites, providing an independent indication of functional 80S in the nucleolus and 80S association with nascent transcripts.

Ribosomal proteins' association with transcription sites peaks at tRNA genes in Schizosaccharomyces pombe.

Ribosomal proteins (RPs) are essential components of ribosomes, but several RPs are also present at transcription sites of eukaryotic chromosomes. Here, we report a genome-wide ChIP-on-chip analysis of the association of three representative 60S RPs with sites in the Schizosaccharomyces pombe chromosomes. All three proteins tend to bind at the same subset of coding and noncoding loci. The data demonstrate selective RNA-dependent interactions between RPs and many transcription sites and suggest that the RPs bind as components of a preassembled multiprotein complex, perhaps 60S or pre-60S subunits. These findings further indicate that the presence of RPs complexes at transcription sites might be a general feature of eukaryotic cells and functionally important. Unexpectedly, the RPs' chromosomal association is highest at centromeres and tRNA genes-the RPs were found at 167 of the 171 tRNA genes assayed. These findings raise the intriguing possibility that RP complexes are involved in tRNA biogenesis and possibly centromere functions.

Resultant inward imbalanced seeding force (RIISF)-induced concave gold nanostar (CAuNS) for non-enzymatic electrocatalytic detection of serotonin and Kynurenine in human serum.

CTAC-based gold nanoseed-induced concave curvature evolution of surface boundary planes from concave gold nanocube (CAuNC) to concave gold nanostar (CAuNS) has been achieved by a novel synthetic methodology simply by controlling the extent of seed used and hence the generated 'Resultant Inward Imbalanced Seeding Force (RIISF)'. The resultant CAuNS shows an excellent enhancement in catalytic activity compared to CAuNC and other intermediates as a function of curvature-induced anisotropy. Detailed characterization evaluates the presence of an enhanced number of multiple defect sites, high energy facets, larger surface area, and roughened surface which ultimately results in an increased mechanical strain, coordinately unsaturation, and multifacet-oriented anisotropic behavior suitable for positive influence on the binding affinity of CAuNSs. While different crystalline and structural parameters improve their catalytic activity, the resultant uniform three-dimensional (3D) platform shows comparatively easy pliability and well absorptivity on the glassy carbon electrode surface for increased shelf life, a uniform structure to confine a large extent of stoichiometric systems, and long-term stability under ambient conditions for making this newly developed material a unique nonenzymatic scalable universal electrocatalytic platform. With the help of various electrochemical measurements, the ability of the platform has been established by performing highly specific and sensitive detection of the two most important human bio messengers: Serotonin (STN) and Kynurenine (KYN) which are metabolites of L-Tryptophan in the human body system. The present study mechanistically surveys the role of seed-induced RIISF-modulated anisotropy in controlling the catalytic activity which offers a universal 3D electrocatalytic sensing tenet by an electrocatalytic approach.

A high-quality Ixodes scapularis genome advances tick science.

Ixodes spp. and related ticks transmit prevalent infections, although knowledge of their biology and development of anti-tick measures have been hindered by the lack of a high-quality genome. In the present study, we present the assembly of a 2.23-Gb Ixodes scapularis genome by sequencing two haplotypes within one individual, complemented by chromosome-level scaffolding and full-length RNA isoform sequencing, yielding a fully reannotated genome featuring thousands of new protein-coding genes and various RNA species. Analyses of the repetitive DNA identified transposable elements, whereas the examination of tick-associated bacterial sequences yielded an improved Rickettsia buchneri genome. We demonstrate how the Ixodes genome advances tick science by contributing to new annotations, gene models and epigenetic functions, expansion of gene families, development of in-depth proteome catalogs and deciphering of genetic variations in wild ticks. Overall, we report critical genetic resources and biological insights impacting our understanding of tick biology and future interventions against tick-transmitted infections.

Deletion of manC in Corynebacterium glutamicum results in a phospho-myo-inositol mannoside- and lipoglycan-deficient mutant.

Mannose is an important constituent of the immunomodulatory glycoconjugates of the mycobacterial cell wall: lipoarabinomannan (LAM), lipomannan (LM) and the related phospho-myo-inositol mannosides (PIMs). In Mycobacterium tuberculosis and the related bacillus Corynebacterium glutamicum, mannose is either imported from the medium or derived from glycolysis, and is subsequently converted into the nucleotide-based sugar donor guanosine diphosphomannose (GDP-mannose). This can be utilized by the glycosyltranferases of the GT-A/B superfamily or converted to the lipid-based donor polyprenyl monophosphomannose, and used as a substrate by the transmembrane glycosyltransferases of the GT-C superfamily. To investigate GDP-mannose biosynthesis in detail, the gene encoding a putative ManC in C. glutamicum was deleted. Deletion of manC resulted in a slow-growing mutant, with reduced but not totally abrogated guanosine diphosphomannose pyrophosphorylase activity. However, a comprehensive cell wall analysis revealed that C. glutamicumΔmanC is deficient in PIMs and LM/LAM. Closer inspection suggests that promiscuous ManC activity is contributed by additional putative nucleotidyltransferases, PmmB, WbbL1, GalU and GlmU, and a hypothetical protein, NCgl0715. Furthermore, complementation analyses of C. glutamicumΔmanC with Rv3264c suggested that it is a true homologue of ManC in M. tuberculosis, and the essentiality of PIMs in M. tuberculosis makes it an attractive drug target.

Learning Design Rules for Selective Oxidation Catalysts from High-Throughput Experimentation and Artificial Intelligence.

The design of heterogeneous catalysts is challenged by the complexity of materials and processes that govern reactivity and by the fact that the number of good catalysts is very small in comparison to the number of possible materials. Here, we show how the subgroup-discovery (SGD) artificial-intelligence approach can be applied to an experimental plus theoretical data set to identify constraints on key physicochemical parameters, the so-called SG rules, which exclusively describe materials and reaction conditions with outstanding catalytic performance. By using high-throughput experimentation, 120 SiO2-supported catalysts containing ruthenium, tungsten, and phosphorus were synthesized and tested in the catalytic oxidation of propylene. As candidate descriptive parameters, the temperature and 10 parameters related to the composition and chemical nature of the catalyst materials, derived from calculated free-atom properties, were offered. The temperature, the phosphorus content, and the composition-weighted electronegativity are identified as key parameters describing high yields toward the value-added oxygenate products acrolein and acrylic acid. The SG rules not only reflect the underlying processes particularly associated with high performance but also guide the design of more complex catalysts containing up to five elements in their composition.

Energy landscape of fullerene materials: a comparison of boron to boron nitride and carbon.

Using the minima hopping global geometry optimization method on the density functional potential energy surface we show that the energy landscape of boron clusters is glasslike. Larger boron clusters have many structures which are lower in energy than the cages. This is in contrast to carbon and boron nitride systems which can be clearly identified as structure seekers. The differences in the potential energy landscape explain why carbon and boron nitride systems are found in nature whereas pure boron fullerenes have not been found. We thus present a methodology which can make predictions on the feasibility of the synthesis of new nanostructures.

Growth and structural properties of Mg(N) (N = 10-56) clusters: density functional theory study.

Using the minima hopping global geometry optimization method on density functional potential energy surface, we have studied the structural and electronic properties of magnesium clusters for a size range of Mg(N) where N = 10-56. Our exhaustive search reveals that most of our global minima are nonsymmetric in the size range above N = 20. We elucidate the evolutionary trend of the entire series and present more details about the peculiar growth of the clusters. For N > 20, it is possible to divide the cluster into two regions: the core region and the surface region. It turns out that the growth follows a peculiar cyclic pattern where the core and surface grow alternatively. The surface energy, as a function of number of atoms shows a clear signature as the number of atoms in the core increases by one. We have also carried out stability analysis and the stable sizes(magic numbers) agree very well with the experimental magic numbers reported by Diederich [J. Chem. Phys. 2011, 134, 124302]. We point out the similarities and differences between our results and sodium clusters.

The effect of ionization on the global minima of small and medium sized silicon and magnesium clusters.

We re-examine the question of whether the geometrical ground state of neutral and ionized clusters are identical. Using a well defined criterion for being "identical" together, the extensive sampling methods on a potential energy surface calculated by density functional theory, we show that the ground states are in general different. This behavior is to be expected whenever there are metastable configurations which are close in energy to the ground state, but it disagrees with previous studies.

Are ribosomal proteins present at transcription sites on or off ribosomal subunits?

RPs (ribosomal proteins) are main components of the ribosome having essential functions in its biogenesis, function and structural integrity. Although most of the RP molecules are in the cytoplasm, being incorporated into translating ribosomes, some RPs have non-ribosomal functions when they are off ribosomal subunits. Notably, in eukaryotes, RPs are also present at transcription sites and some of these proteins have a function in transcription and pre-mRNA processing of specific genes. Although the consensus is that the proteins found at these sites are isolated RPs not assembled into ribosomal subunits, it has been proposed that ribosomal subunits might also be present. In the present paper, we review the available evidence for RPs at transcription sites and conclude that ribosomal subunits might be present, but additional studies will be required to solve this important issue.

Defining the Boundaries of Polycomb Domains in Drosophila.

Polycomb group (PcG) proteins are an important group of transcriptional repressors that act by modifying chromatin. PcG target genes are covered by the repressive chromatin mark H3K27me3. Polycomb repressive complex 2 (PRC2) is a multiprotein complex that is responsible for generating H3K27me3. In Drosophila, PRC2 is recruited by Polycomb Response Elements (PREs) and then trimethylates flanking nucleosomes, spreading the H3K27me3 mark over large regions of the genome, the "Polycomb domains." What defines the boundary of a Polycomb domain? There is experimental evidence that insulators, PolII, and active transcription can all form the boundaries of Polycomb domains. Here we divide the boundaries of larval Polycomb domains into six different categories. In one category, genes are transcribed toward the Polycomb domain, where active transcription is thought to stop the spreading of H3K27me3. In agreement with this, we show that introducing a transcriptional terminator into such a transcription unit causes an extension of the Polycomb domain. Additional data suggest that active transcription of a boundary gene may restrict the range of enhancer activity of a Polycomb-regulated gene.

Machine Learning-Guided Approach for Studying Solvation Environments.

Molecular-level understanding and characterization of solvation environments are often needed across chemistry, biology, and engineering. Toward practical modeling of local solvation effects of any solute in any solvent, we report a static and all-quantum mechanics-based cluster-continuum approach for calculating single-ion solvation free energies. This approach uses a global optimization procedure to identify low-energy molecular clusters with different numbers of explicit solvent molecules and then employs the smooth overlap for atomic positions learning kernel to quantify the similarity between different low-energy solute environments. From these data, we use sketch maps, a nonlinear dimensionality reduction algorithm, to obtain a two-dimensional visual representation of the similarity between solute environments in differently sized microsolvated clusters. After testing this approach on different ions having charges 2+, 1+, 1-, and 2-, we find that the solvation environment around each ion can be seen to usually become more similar in hand with its calculated single-ion solvation free energy. Without needing either dynamics simulations or an a priori knowledge of local solvation structure of the ions, this approach can be used to calculate solvation free energies within 5% of experimental measurements for most cases, and it should be transferable for the study of other systems where dynamics simulations are not easily carried out.