bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Flagellin Proteins Have Distinct and Synergistic Roles inAgrobacterium tumefaciensMotility
Authors: Mohari Bitan , Thompson Melene A. , Trinidad Jonathan C , Fuqua Clay
Published: May 2018

Rotary flagella propel bacteria through liquid and across semi-solid environments. Flagella are composed of the basal body that constitutes the motor for rotation, the curved hook that connects to the basal body, and the flagellar filament that propels the cell. Flagellar filaments can be comprised of a single flagellin protein such as inEscherichia colior with multiple flagellins such is inAgrobacterium tumefaciens. The four distinct flagellins FlaA, FlaB, FlaC and FlaD produced by wild typeA. tumefaciens, are not redundant in function, but have specific properties. FlaA and FlaB are much more abundant than FlaC and FlaD and are readily observable in mature flagellar filaments, when either FlaA or FlaB is fluorescently labeled. Cells having FlaA with any one of the other three flagellins can generate functional filaments and thus are motile, but FlaA alone cannot constitute a functional filament. InflaAmutants that manifest swimming deficiencies, there are multiple ways by which these mutations can be phenotypically suppressed. These suppressor mutations primarily occur within or upstream of theflaBflagellin gene or in the transcriptional factorsciPregulating flagellar expression. The helical conformation of the flagellar filament appears to require a key asparagine residue present in FlaA and absent in other flagellins. However, FlaB can be spontaneously mutated to render helical flagella in absence of FlaA, reflecting their overall similarity and perhaps the subtle differences in the specific functions they have evolved to fulfill.

Importance

Flagellins are abundant bacterial proteins comprising the flagellar filaments that propel bacterial movement. Several members of the Alphaproteobacterial group express multiple flagellins, in contrast to model systems such asEscherichia colithat has only one flagellin protein. The plant pathogenAgrobacterium tumefacienshas four flagellins, the abundant and readily detected FlaA and FlaB, and lower levels of FlaC and FlaD. Mutational analysis reveals that FlaA requires at least one of the other flagellins to function -flaAmutants produce non-helical flagella and cannot swim efficiently. Suppressor mutations can rescue this swimming defect through mutations in the remaining flagellins, including structural changes imparting flagellar helical shape, and putative regulators. Our findings shed light on how multiple flagellins contribute to motility.
Virus-Like Particles and Magnetic Microspheres Provide a Flexible and Sustainable Multiplexed Alphavirus Immunodiagnostic Platform
Authors: Ricks Keersten M. , Shoemaker Charles J. , Dupuy Lesley C. , Flusin Olivier , Voorhees Matthew A. , Fulmer Ashley N. , Six Carolyn M. , Badger Catherine V. , Schmaljohn Connie S. , Schoepp Randal J.
Published: May 2018

There is a pressing need for sustainable and sensitive immunodiagnostics for use in public health efforts to understand and combat the threat of endemic and emerging infectious diseases. We describe a novel approach to immunodiagnostics based on virus-like particles (VLPs) attached to magnetic beads. This flexible, innovative immunoassay system, based on the MAGPIX® platform, improves sensitivity by up to 2-logs and has faster sample-to-answer time over traditional methods. As a proof of concept, a retroviral-based VLP, that presents the Venezuelan equine encephalitis virus E1/E2 glycoprotein antigen on its surface, was generated and coupled to magnetic beads to create VLP-conjugated microspheres (VCMs). Using these VCMs, IgG and IgM antibodies were detectable in nonhuman primate (NHP) and human clinical serum samples at dilutions of 1 × 104 and greater. We extended the VCM methodology to two other New-World alphaviruses, eastern and western equine encephalitis viruses, as well as an Old-World alphavirus, Chikungunya virus, demonstrating the flexibility of this approach toward different VLP architectures. When multiplexed on the MAGPIX® platform, the VCMs provided differential diagnosis between Old-World and New-World alphaviruses and well as a route toward assessing the humoral response to both natural infection and vaccination. This VCM system will allow more rapid and efficient detection of endemic and emerging viral pathogens in human populations.
Cell shape independent FtsZ dynamics in synthetically remodeled cells
Authors: Söderström Bill , Badrutdinov Alexander , Chan Helena , Skoglund Ulf
Published: May 2018

The FtsZ protein is a key regulator of bacterial cell division. It has been implicated in acting as a scaffolding protein for other division proteins, being a force generator during constriction, and more recently, as an active regulator of septal cell wall production. During an early stage of the division cycle, FtsZ assembles into a heterogeneous structure coined the “Z-ring” due to its resemblance to a ring confined by the midcell geometry. Whilein vitroexperiments on supported lipid bilayers have shown that purified FtsZ can self-organize into a swirling ring roughly the diameter of a bacterial cell, it is not known how, and if, membrane curvature affects FtsZ assembly and dynamicsin vivo.

To establish a framework for examining geometrical influences on proper Z-ring assembly and dynamics, we sculpturedEscherichia colicells into unnatural shapes, such as squares and hearts, using division- and cell wall-specific inhibitors in a micro fabrication scheme. This approach allowed us to examine FtsZ behavior in engineered “Z-squares” and “Z-hearts”, and in giant cells up to 50 times their normal volume. Quantification of super-resolution STimulated Emission Depletion (STED) nanoscopy data showed that FtsZ densities in sculptured cells maintained the same dimensions as their wild-type counterparts. Additionally, time-resolved fluorescence measurements revealed that FtsZ dynamics were generally conserved in a wide range of cell shapes. Based on our results, we conclude that the underlying membrane environment is not a deciding factor for FtsZ filament maintenance and treadmillingin vivo.
Widespread inter-individual gene expression variability inArabidopsis thaliana
Authors: Cortijo Sandra , Aydin Zeynep , Ahnert Sebastian , Locke James
Published: May 2018

A fundamental question in biology is how gene expression is regulated to give rise to a phenotype. However, transcriptional variability is rarely considered and could influence the relationship between genotype and phenotype. It is known in unicellular organisms that gene expression is often noisy rather than uniform and this has been proposed to be beneficial when environmental conditions are unpredictable. However, little is known about transcriptional variability in plants. Using transcriptomic approaches, we analysed gene expression variability between individualArabidopsis thalianaplants growing in identical conditions over a 24 hour time-course. We identified hundreds of genes that exhibit high inter-individual variability and found that many are involved in environmental responses. We also identified factors that might facilitate gene expression variability, such as gene length, the number of transcription factors regulating the genes and the chromatin environment. These results shed new light on the impact of transcriptional variability in gene expression regulation in plants.
Biophysical basis of alpha rhythm disruption in Alzheimer’s disease
Authors: Sharma Rohan , Nadkarni Suhita
Published: May 2018

Alpha is one of the most prominent rhythms (7.5–12.5 Hz) detected in electroencephalography (EEG) during wakeful relaxation with closed eyes. In response to elevated ambient acetylcholine levels, a subclass of thalamic pacemaker cells generate alpha. This rhythm is intrinsic to the cell and is robustly orchestrated by an interplay of hyperpolarization activated cyclic nucleotide gated channels(HCN) and calcium-ion channels. It has been shown that decreased expression of HCN channels is correlated to Alzheimer's Diseased (AD). In early stages of AD, alpha is known to be down-regulated and lowered in coherence. We use this well characterized and quantified rhythm to understand the changes in ion channel properties that lead to disruption of alpha as seen in AD in a biophysically detailed network model of the thalamo-cortical circuit that generates the alpha-rhythm. Our computational model allows us to explore the causal links between alpha rhythms, HCN channels and amyloid-beta aggregation. The most commonly used drugs(acetylcholinesterase inhibitors) in AD increase the duration and level of acetylcholine and provide temporary symptomatic relief in some cases. Our simulations show how increasing acetylcholine can provide rescue for a small range of aberrant HCN expression. We hypothesize that reduced alpha rhythm frequency and coherence is a result of down-regulated HCN expression, rather then compromised cholinergic modulation(as is currently thought). The model predicts that lowering of the alpha-rhythm can modify the network activity in the thalamo-cortical circuit and lead to an increase in the inhibitory drive to the thalamus.
The scent of symbiosis: gut bacteria affect social interactions in leafcutting ants
Authors: Teseo Serafino , van Zweden Jelle S. , Pontieri Luigi , Kooij Pepijn W. , Sørensen Søren J. , Wenseleers Tom , Poulsen Michael , Boomsma Jacobus J. , Sapountzis Panagiotis
Published: May 2018

Animal gut microbiota affect host physiology and behaviour. In eusocial Hymenoptera, where colony-level integrity is preserved via a nestmate discrimination system based on cuticular hydrocarbon mixtures, microorganismal effects may influence social dynamics. Although nestmate recognition has undergone a thorough exploration during the last four decades, few studies have investigated the putative role of gut microbes. Here we integrate metagenomic, chemical and behavioural approaches to test whether gut microbes affect nestmate recognition inAcromyrmex echinatiorleaf-cutting ants. Treating workers with a sterile diet or with antibiotics resulted in a substantial alteration of their gut microbial communities. In pairwise social interactions, untreated vs. antibiotic-treated nestmates behaved more aggressively than other nestmate and non-nestmate pairs, suggesting that the suppression of microbes indirectly alters chemical social cues and triggers aggressive behaviour. Chemical analyses on treated individuals revealed a decrease in the abundance of two metapleural gland antifungal compounds, and we confirmed the correspondence between aggression levels and chemical profile differences. Feeding microbiota-remodelled ants with conspecific faecal droplets partially restored the original bacterial communities. Furthermore, non-nestmates fed with faecal droplets from different colonies were unusually aggressive compared to pairs fed with faecal droplets from the same colony. This suggests that chemicals derived from microbial strains may shape nestmate recognition, opening novel questions about the role of microorganisms in the evolution of social behaviour.
CellTag Indexing: genetic barcode-based sample multiplexing for single-cell genomics
Authors: Guo Chuner , Kong Wenjun , Kamimoto Kenji , Rivera-Gonzalez Guillermo C. , Yang Xue , Kirita Yuhei , Morris Samantha A
Published: May 2018

Single-cell technologies have seen rapid advancements in recent years, presenting new analytical challenges and opportunities. These high-throughput assays increasingly require special consideration in experimental design, sample multiplexing, batch effect removal, and data interpretation. Here, we describe a lentiviral barcode-based multiplexing approach, ‘CellTag Indexing’, where we transduce and label samples that can then be pooled together for downstream experimentation and analysis. By introducing predefined genetic barcodes that are transcribed and readily detected, we can reliably read out sample identity and transcriptional state via single-cell profiling. We validate and demonstrate the utility of CellTag Indexing by sequencing transcriptomes at single-cell resolution using a variety of cell types including mouse pre-B cells, primary mouse embryonic fibroblasts, and human HEK293T cells. A unique feature of CellTag Indexing is that the barcodes are heritable. This enables cell populations to be tagged, pooled and tracked over time within the same experimental replicate, then processed together to minimize unwanted biological and technical variation. We demonstrate this feature of CellTagging in long-term tracking of cell engraftment and differentiation, in vivo, in a mouse model of competitive transplant into the large intestine. Together, this presents CellTag Indexing as a broadly applicable genetic multiplexing tool that is complementary with existing single-cell technologies.
Bile acids target proteolipid nano-assemblies of EGFR and phosphatidic acid in the plasma membrane for stimulation of MAPK signaling
Authors: Liang Hong , Estes Mary K. , Zhang Huiling , Du Guangwei , Zhou Yong
Published: May 2018

Bile acids are critical biological detergents in the gastrointestinal tract and also act as messengers to regulate a multitude of intracellular signaling events, including mitogenic signaling, lipid metabolism and endo/exocytosis. In particular, bile acids stimulate many receptors and ion channels on the cell surface, the mechanisms of which are still poorly understood. Membrane-associating proteins depend on the local spatial distribution of lipids in the plasma membrane (PM) for their function. Here, we report that the highly amphipathic secondary bile acid deoxycholic acid (DCA), a major constituent in the human bile, at doses <1μM enhances the nanoclustering of phosphatidic acid (PA) but disrupts the local segregation of phosphoinositol 4,5-bisphosphate (PIP2) in the basolateral PM of the human colorectal adenocarcinoma Caco-2 cells. PA has been shown to be a key structural component of the signaling nano-domains of epidermal growth factor receptor (EGFR) on the cell surface. We show that DCA promotes the co-localization between PA and EGFR, the PA-driven EGFR dimerization/oligomerization and EGFR signaling. Depletion of PA abolishes the stimulatory effects of DCA on the EGFR oligomerization and signaling. This effect occurs in the cultured Caco-2 cells and the ex vivo human intestinal enteroids. We propose a novel mechanism, where the amphiphilic DCA monomers alter the nano-assemblies of anionic phospholipids and in turn change the dynamic structural integrity of the lipid-driven oligomerization of cell surface receptors and their signal transduction.
CRISPR-Cas9 interrogation of a putative fetal globin repressor in human erythroid cells
Authors: Chung Jennifer , Magis Wendy , Vu Jonathan , Heo Seok-Jin , Wartiovaara Kirmo , Walters Mark C. , Kurita Ryo , Nakamura Yukio , Boffelli Dario , Martin David I. K. , Corn Jacob E. , Dewitt Mark A.
Published: May 2018

Sickle Cell Disease and ß-thalassemia, which are caused by defective or deficient adult ß-globin (HBB) respectively, are the most common serious genetic blood diseases in the world. Expression of the fetal ß-like globin, also known as γ-globin, can ameliorate both disorders by serving in place of the adult ß-globin. Here we use CRISPR-Cas9 gene editing to explore a putative γ-globin silencer region identified by comparison of naturally-occurring deletion mutations associated with up-regulated γ-globin. We find that deletion of a 1.7 kb consensus element or select 350 bp sub-regions from bulk populations of cells increases levels of fetal hemoglobin (HbF) or γ-globin. Screening of individual sgRNAs in one sub-region revealed three single guides that caused mild increases in γ-globin expression. However, clonal cell lines with the 1.7 kb region deleted did not up-regulate γ-globin and neither did lines with either of two of sub-regions identified in the screen deleted. These data suggest that the region is not an autonomous γ-globin silencer, and thus by itself is not a suitable therapeutic target in the ß-hemoglobinopathies.
Identification of biological mechanisms by semantic classifier systems
Authors: Lausser Ludwig , Schmid Florian , Siegle Lea , Hühne Rolf , Buchholz Malte , Kestler Hans A.
Published: May 2018

The interpretability of a classification model is one of its most essential characteristics. It allows for the generation of new hypotheses on the molecular background of a disease. However, it is questionable if more complex molecular regulations can be reconstructed from such limited sets of data. To bridge the gap between complexity and interpretability, we replace the de novo reconstruction of these processes by a hybrid classification approach partially based on existing domain knowledge. Using semantic building blocks that reflect real biological processes these models were able to construct hypotheses on the underlying genetic configuration of the analysed phenotypes. As in the building process, also these hypotheses are composed of high-level biology-based terms. The semantic information we utilise from gene ontology is a vocabulary which comprises the essential processes or components of a biological system. The constructed semantic multi-classifier system consists of expert base classifiers which each select the most suitable term for characterising their assigned problems. Our experiments conducted on datasets of three distinct research fields revealed terms with well-known associations to the analysed context. Furthermore, some of the chosen terms do not seem to be obviously related to the issue and thus lead to new, hypotheses to pursue.

Author summary

Data mining strategies are designed for an unbiased de novo analysis of large sample collections and aim at the detection of frequent patterns or relationships. Later on, the gained information can be used to characterise diagnostically relevant classes and for providing hints to the underlying mechanisms which may cause a specific phenotype or disease. However, the practical use of data mining techniques can be restricted by the available resources and might not correctly reconstruct complex relationships such as signalling pathways.

To counteract this, we devised a semantic approach to the issue: a multi-classifier system which incorporates existing biological knowledge and returns interpretable models based on these high-level semantic terms. As a novel feature, these models also allow for qualitative analysis and hypothesis generation on the molecular processes and their relationships leading to different phenotypes or diseases.
Energy conservation via hydrogen cycling in the methanogenic archaeonMethanosarcina barkeri
Authors: Kulkarni Gargi , Mand Thomas D. , Metcalf William W.
Published: May 2018

Energy conservation via hydrogen cycling, which generates proton motive force by intracellular H2production coupled to extracellular consumption, has been controversial since it was first proposed in 1981. It was hypothesized that the methanogenic archaeonMethanosarcina barkeriis capable of energy conservation via H2cycling, based on genetic data that suggest H2is a preferred, but non-essential, intermediate in the electron transport chain of this organism. Here, we characterize a series of hydrogenase mutants to provide direct evidence of H2cycling.M. barkeriproduces H2during growth on methanol, a phenotype that is lost upon mutation of the cytoplasmic hydrogenase encoded byfrhADGB, although low levels of H2, attributable to the Ech hydrogenase, accumulate during stationary phase. In contrast, mutations that conditionally inactivate the extracellular Vht hydrogenase are lethal when expression of thevhtGACDoperon is repressed. Under these conditions H2accumulates, with concomitant cessation of methane production and subsequent cell lysis, suggesting that the inability to recapture extracellular H2is responsible for the lethal phenotype. Consistent with this interpretation, double mutants that lack both Vht and Frh are viable. Thus, when intracellular hydrogen production is abrogated, loss of extracellular H2consumption is no longer lethal. The common occurrence of both intracellular and extracellular hydrogenases in anaerobic microorganisms suggests that this unusual mechanism of energy conservation may be widespread in nature.

Importance

Adenosine triphosphate (ATP) is required by all living organisms to facilitate essential endergonic reactions required for growth and maintenance. Although synthesis of ATP by substrate-level phosphorylation is widespread and significant, most ATP is made via the enzyme ATP synthase, which is energized by transmembrane chemiosmotic gradients. Therefore, establishing this gradient across the membrane is of central importance to sustaining life. Experimental validation of H2cycling adds to a short list of mechanisms for generating a transmembrane electrochemical gradient that is likely to be widespread, especially among anaerobic microorganisms.
Nothing else matters? Tree characteristics have more effects than biogeoclimatic context on microhabitat diversity and occurrence: a nationwide analysis
Authors: Paillet Yoan , Debaive Nicolas , Archaux Frédéric , Cateau Eugénie , Gilg Olivier , Guilbert Eric
Published: May 2018

Managing forests to preserve biodiversity requires a good knowledge not only of the factors driving its dynamics but also of the structural elements that actually support biodiversity. Tree-related microhabitats (cavities, cracks, conks of fungi) are tree-borne features that are reputed to support specific biodiversity for at least a part of species’ life cycles. While several studies have analysed the drivers of microhabitats number and occurrence at the tree scale, they remain limited to a few tree species located in relatively narrow biogeographical ranges. We used a nationwide database of forest reserves where microhabitats were inventoried on more than 22,000 trees. We analysed the effect of tree diameter and living status (alive or dead) on microhabitat number and occurrence per tree, taking into account biogeoclimatic variables and tree genus.

We confirmed that larger trees and dead trees bore more microhabitats than their smaller or living counterparts did; we extended these results to a wider range of tree genera and ecological conditions. Contrary to expectations, the total number of microhabitat types per tree barely varied with tree genus – though we did find slightly higher accumulation levels for broadleaves than for conifers – nor did it vary with elevation or soil pH. We observed the same results for the occurrence of individual microhabitat types. However, accumulation levels with diameter and occurrence on dead trees were higher for microhabitats linked with wood decay processes (e.g. dead branches or woodpecker feeding holes) than for other, epixylic, microhabitats such as epiphytes (ivy, mosses and lichens).

Promoting large living and dead trees of several tree species may be an interesting, and nearly universal, way to favour microhabitats and enhance the substrates needed to support specific biodiversity. In addition, a better understanding of microhabitat drivers and dynamics at the tree scale may help to better define their role as biodiversity indicators for large-scale monitoring.
Available energy fluxes drive a transition in the diversity, stability, and functional structure of microbial communities
Authors: Marsland Robert , Cui Wenping , Goldford Joshua , Sanchez Alvaro , Korolev Kirill , Mehta Pankaj
Published: May 2018

A fundamental goal of microbial ecology is to understand what determines the diversity, stability, and structure of microbial ecosystems. The microbial context poses special conceptual challenges because of the strong mutual influences between the microbes and their chemical environment through the consumption and production of metabolites. By analyzing a generalized consumer resource model that explicitly includes cross-feeding, stochastic colonization, and thermodynamics, we show that complex microbial communities generically exhibit a transition as a function of available energy fluxes from a “resource-limited” regime where community structure and stability is shaped by energetic and metabolic considerations to a diverse regime where the dominant force shaping microbial communities is the overlap between species’ consumption preferences. These two regimes have distinct species abundance patterns, different functional profiles, and respond differently to environmental perturbations. Our model reproduces large-scale ecological patterns observed across multiple experimental settings such as nestedness and differential beta diversity patterns along energy gradients. We discuss the experimental implications of our results and possible connections with disorder-induced phase transitions in statistical physics.
Continuous embeddings of DNA sequencing reads, and application to metagenomics
Authors: Menegaux Romain , Vert Jean-Philippe
Published: May 2018

We propose a new model for fast classification of DNA sequences output by next generation sequencing machines. The model, which we call fastDNA, embeds DNA sequences in a vector space by learning continuous low-dimensional representations of the k-mers it contains. We show on metagenomics benchmarks that it outperforms state-of-the-art methods in terms of accuracy and scalability.
Vasculature-associated adipose tissue macrophages dynamically adapt to inflammatory and metabolic challenges
Authors: Silva Hernandez Moura , Báfica André , Rodrigues-Luiz Gabriela Flavia , Chi Jingyi , Alves Santos Patricia d’Emery , Reis Bernardo S. , Hoytema van Konijnenburg David P. , Crane Audrey , Nascimento Arifa Raquel Duque , Martin Patricia , Mendes Daniel Augusto G.B. , Mansur Daniel Santos , Torres Victor , Cadwell Ken , Cohen Paul , Mucida Daniel , Lafaille Juan José
Published: May 2018

Tissue-resident macrophages comprise the most abundant immune cell population in healthy adipose tissue. Adipose tissue macrophage populations change during metabolic stress and ageing, and are thought to contribute to the pathogenesis of obesity. Here, we studied adipose tissue macrophage subpopulations in the steady state, and in response to nutritional and infectious challenges.

Using comprehensive cell-surface-based and gene expression analyses, we found that tissue-resident macrophages from healthy epididymal white adipose tissue (eWAT) tightly associate with blood vessels, displaying a very high endocytic capacity. We refer to these cells as Vasculature-associated Adipose tissue Macrophages (VAMs). Chronic high fat diet (HFD) feeding results in the accumulation of a monocyte-derived CD11c+CD64+double positive (DP) macrophage eWAT population with a predominant anti-inflammatory gene profile, but reduced endocytic function. In contrast, fasting rapidly and reversibly leads to VAM depletion, while acute inflammatory stress induced by pathogens transiently depletes VAMs and simultaneously boosts DP macrophage accumulation. Our results indicate that adipose tissue macrophage populations adapt to metabolic stress and inflammation, suggesting an important role for these cells in restoring homeostasis.
Anti-diuretic activity of a CAPA neuropeptide can compromiseDrosophilachill tolerance
Authors: MacMillan Heath A. , Nazal Basma , Wali Sahr , Yerushalmi Gil Y. , Misyura Lidiya , Donini Andrew , Paluzzi Jean-Paul
Published: May 2018

For insects, chilling injuries that occur in the absence of freezing are often related to a systemic loss of ion and water balance that leads to extracellular hyperkalemia, cell depolarization, and the triggering of apoptotic signalling cascades. The ability of insect ionoregulatory organs (e.g. the Malpighian tubules) to maintain ion balance in the cold has been linked to improved chill tolerance, and many neuroendocrine factors are known to influence ion transport rates of these organs. Injection of micromolar doses of CAPA (an insect neuropeptide) have been previously demonstrated to improveDrosophilacold tolerance, but the mechanisms through which it impacts chill tolerance are unclear, and low doses of CAPA have been demonstrated to cause anti-diuresis in other insects, including dipterans. Here, we provide evidence that low (fM) and high (µM) doses of CAPA impair and improve chill tolerance, respectively,viatwo different effects on Malpighian tubule ion and water transport. While low doses of CAPA are anti-diuretic, reduce tubule K+clearance rates and reduce chill tolerance, high doses facilitate K+clearance from the haemolymph and increase chill tolerance. By quantifying CAPA peptide levels in the central nervous system, we estimated the maximum achievable hormonal titres of CAPA, and found evidence to suggest that CAPA may function as an anti-diuretic peptide inDrosophila. We provide the first evidence of a neuropeptide that can negatively affect cold tolerance in an insect, and the first evidence of CAPA as an anti-diuretic peptide in this ubiquitous insect model.

Summary Statement

Many insects ion balance in the cold. We show how one neuropeptide can slow ion transport and reduce the cold tolerance of a fly.
The Unreasonable Effectiveness of Convolutional Neural Networks in Population Genetic Inference
Authors: Flagel Lex , Brandvain Yaniv , Schrider Daniel R.
Published: May 2018

Population-scale genomic datasets have given researchers incredible amounts of information from which to infer evolutionary histories. Concomitant with this flood of data, theoretical and methodological advances have sought to extract information from genomic sequences to infer demographic events such as population size changes and gene flow among closely related populations/species, construct recombination maps, and uncover loci underlying recent adaptation. To date most methods make use of only one or a few summaries of the input sequences and therefore ignore potentially useful information encoded in the data. The most sophisticated of these approaches involve likelihood calculations, which require theoretical advances for each new problem, and often focus on a single aspect of the data (e.g. only allele frequency information) in the interest of mathematical and computational tractability. Directly interrogating the entirety of the input sequence data in a likelihood-free manner would thus offer a fruitful alternative. Here we accomplish this by representing DNA sequence alignments as images and using a class of deep learning methods called convolutional neural networks (CNNs) to make population genetic inferences from these images. We apply CNNs to a number of evolutionary questions and find that they frequently match or exceed the accuracy of current methods. Importantly, we show that CNNs perform accurate evolutionary model selection and parameter estimation, even on problems that have not received detailed theoretical treatments. Thus, when applied to population genetic alignments, CNN are capable of outperforming expert-derived statistical methods, and offer a new path forward in cases where no likelihood approach exists.
Proteomic Analysis of ACE Inhibitory Peptides extracted from Fermented Goat Milk
Authors: Aslam Muhammad Zohaib , Shoukat Sana , Hongfei Zhao , Bolin Zhang
Published: May 2018

Protein extracted from goat milk was hydrolyzed with LH (Lactobacillus Helveticus-cicc22171). Angiotensin Converting Enzyme (ACE) inhibitory peptides were purified from fermented samples of goat milk protein with LH by optimizing incubation time to 8 hours (S-8), 16 hours (S-16), 24 hours (S-24) and 36 hours (S-36), via ultrafiltration. Molecular weight cut-off; 10000 Da (PM-10) membrane was used to perform size exclusion chromatography. Sample with 24 h incubation time was considered as best hydrolyzed as compared to others, by applying Nin-Hydrin reaction and SDS-PAGE analysis. ACE inhibitory assay validated the authenticity of S-24 in inhibiting ACE, in vitro. Furthermore, Q executive Hybrid Quadrapole-Orbitrap Mass Spectrometry was used to determine molecular structure and amino acid sequence of ACE inhibitory peptides. Two protein groups VLPVPQKAVPQ and VLPVPQKVVPQ containing PVP, VVP along with one most abundant peptide TQTPVVVPPFLQPEIMGVPKVKE containing VPP has been identified with highest ACE inhibitory activity on the basis of intensity, small structure and higher concentration of hydrophobic and aromatic amino acids. Fermented goat milk containing these novel bioactive peptides, can be used as nutraceuticals to inhibit ACE and control hypertension.
Principal Component Analysis applied directly to Sequence Matrix
Authors: Konishi Tomokazu , Matsukuma Shiori , Fuji Hayami , Nakamura Daiki , Satou Nozomi , Okano Kunihiko
Published: May 2018

Sequence data is now widely used to observe relationships among organisms. However, understanding structure of the qualitative data is challenging. Conventionally, the relationships are analyzed using a dendrogram that estimates a tree shape. This approach has difficulty in verifying the appropriateness of the tree shape; rather, horizontal gene transfers and mating can make the shape of the relationship as networks. As a connection-free approach, principal component analysis (PCA) is used to summarize the distance matrix, which records distances between each combination of samples. However, this approach is limited regarding the treatment of information of sequence motifs; distances caused by different motifs are mixed up. This hides clues to figure out how the samples are different. As any bases may change independently, sequence is multivariate data essentially. Hence, differences among samples and bases that contribute to the difference should be observed coincidentally. To archive this, the sequence matrix is transferred to boolean vector and directly analyzed by using PCA. The effects are confirmed in diversity of Asiatic lion and human as well as environmental DNA. Resolution of samples and robustness of calculation is improved. Relationship of a direction of difference and causative nucleotides has become obvious at a glance.
Diurnal Chorusing in Nine Species of North American Frogs
Authors: McCallum Malcolm L. , McCallum Jamie L.
Published: May 2018

A year-long survey of survey of diurnal frog calling behavior was conducted at the Red River Research and Education Park in Shreveport (Caddo Parish), Louisiana to investigate the prevalence of daytime breeding choruses in the species present at the park. We determined that 60% (9/15) of species known from the area participated in daytime breeding choruses. Four of these were new species reports for the behavior. One species was identified entirely based on a daytime chorus from outside the normal breeding season. Although we believe daytime chorusing is widespread in frogs, several species did not diurnally chorus during our study. Diurnal calling may be an important indicator of the peak breeding season for a species and it may also be a useful tool at times when night surveys are impossible.
Enhancement of Transgene Expression by NF-Y and CTCF
Authors: Zimmerman Devon , Patel Krupa , Hall Matthew , Elmer Jacob
Published: May 2018

If a transgene is effectively delivered to a cell, its expression may still be limited by epigenetic mechanisms that silence the transgene. Indeed, once the transgene reaches the nucleus, it may be bound by histone proteins and condensed into heterochromatin or associated with repressor proteins that block transcription. In this study, we sought to enhance transgene expression by adding binding motifs for several different epigenetic enzymes either upstream or downstream of two promoters (CMV and EF1α). Screening these plasmids revealed that luciferase expression was enhanced 10-fold by the addition of a CCAAT box just upstream of the EF1α promoter to recruit nuclear transcription factor Y (NF-Y), while inserting a CCCTC-binding factor (CTCF) motif downstream of the EF1α promoter enhanced expression 14-fold (14.03 ± 6.54). ChIP assays confirmed that NF-Y and CTCF bound to the motifs that were added to each plasmid, but the presence of NF-Y and CTCF did not significantly affect the levels of histone acetylation (H3K9ac). Overall, these result show that transgene expression from the EF1α promoter can be significantly increased with motifs that recruit NF-Y or CTCF.
Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
Authors: Benayoun Bérénice A. , Pollina Elizabeth A. , Singh Param Priya , Mahmoudi Salah , Harel Itamar , Casey Kerriann M. , Dulken Ben W. , Kundaje Anshul , Brunet Anne
Published: May 2018

Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here we generated chromatin maps and transcriptomes from 4 tissues and one cell type from young, middle-age, and old mice, yielding 143 high-quality datasets. We focused specifically on chromatin marks linked to gene expression regulation and cell identity: histone H3 trimethylation at lysine 4 (H3K4me3), a mark enriched at promoters, and histone H3 acetylation at lysine 27 (H3K27ac), a mark enriched at active enhancers. Epigenomic and transcriptomic landscapes could easily distinguish between ages, and machine learning analysis showed that specific epigenomic states could predict transcriptional changes during aging. Analysis of datasets from all tissues identified recurrent age-related chromatin and transcriptional changes in key processes, including the upregulation of immune system response pathways such as the interferon signaling pathway. The upregulation of interferon response pathway with age was accompanied by increased transcription of various endogenous retroviral sequences. Pathways deregulated during mouse aging across tissues, notably innate immune pathways, were also deregulated with aging in other vertebrate species – African turquoise killifish, rat, and humans – indicating common signatures of age across species. To date, our dataset represents the largest multi-tissue epigenomic and transcriptomic dataset for vertebrate aging. This resource identifies chromatin and transcriptional states that are characteristic of youthful tissues, which could be leveraged to restore aspects of youthful functionality to old tissues.
Scandium complexes with the tetraphenylethylene and anthracene dianions
Authors: Ellis John E. , Minyaev Mikhail E. , Nifant'ev Ilya E. , Churakov Andrei V.
Published: May 2018

The structural study of Sc complexes containing dianions of anthracene and tetraphenylethylene should shed some light on the nature of rare-earth metal–carbon bonding. The crystal structures of (18-crown-6)bis(tetrahydrofuran-κO)sodium bis(η6-1,1,2,2-tetraphenylethenediyl)scandium(III) tetrahydrofuran disolvate, [Na(C4H8O)2(C12H24O6)][Sc(C26H20)2]·2C4H8O or [Na(18-crown-6)(THF)2][Sc(η6-C2Ph4)2]·2(THF), (1b), (η5-1,3-diphenylcyclopentadienyl)(tetrahydrofuran-κO)(η6-1,1,2,2-tetraphenylethenediyl)scandium(III) toluene hemisolvate, [Sc(C17H13)(C26H20)(C4H8O)]·0.5C7H8or [(η5-1,3-Ph2C5H3)Sc(η6-C2Ph4)(THF)]·0.5(toluene), (5b), poly[[(μ2-η3:η3-anthracenediyl)bis(η6-anthracenediyl)bis(η5-1,3-diphenylcyclopentadienyl)tetrakis(tetrahydrofuran)dipotassiumdiscandium(III)] tetrahydrofuran monosolvate], {[K2Sc2(C14H10)3(C17H13)2(C4H8O)4]·C4H8O}nor [K(THF)2]2[(1,3-Ph2C5H3)2Sc2(C14H10)3]·THF, (6), and 1,4-diphenylcyclopenta-1,3-diene, C17H14, (3a), have been established. The [Sc(η6-C2Ph4)2]−complex anion in (1b) contains the tetraphenylethylene dianion in a symmetrical bis-η3-allyl coordination mode. The complex homoleptic [Sc(η6-C2Ph4)2]−anion retains its structure in THF solution, displaying hindered rotation of the coordinated phenyl rings. The 1D1H and13C{1H}, and 2D COSY1H–1H and13C–1H NMR data are presented forM[Sc(Ph4C2)2]·xTHF [M= Na andx= 4 for (1a);M= K andx= 3.5 for (2a)] in THF-d8media. Complex (5b) exhibits an unsymmetrical bis-η3-allyl coordination mode of the dianion, but this changes to a η4coordination mode for (1,3-Ph2C5H3)Sc(Ph4C2)(THF)2, (5a), in THF-d8solution. A45Sc NMR study of (2a) and UV–Vis studies of (1a), (2a) and (5a) indicate a significant covalent contribution to the Sc—Ph4C2bond character. The unique Sc ate complex, (6), contains three anthracenide dianions demonstrating both a η6-coordination mode for two bent ligands and a μ2-η3:η3-bridging mode of a flat ligand. Each [(1,3-Ph2C5H3)2Sc2(C14H10)3]2−dianionic unit is connected to four neighbouring unitsviashort contacts with [K(THF)2]+cations, forming a two-dimensional coordination polymer framework parallel to (001).
PsEst3, a new psychrophilic esterase from the Arctic bacterium Paenibacillus sp. R4: crystallization and X-ray crystallographic analysis
Authors: Kim Hyun , Park Ae Kyung , Lee Jun Hyuck , Shin Seung Chul , Park Hyun , Kim Han-Woo
Published: May 2018

Esterases are very useful biocatalysts in industry: they hydrolyze esters and split them into a carboxylic acid and an alcohol. The psychrophilic esterase PsEst3 was obtained from Paenibacillus sp. R4, which was isolated from the active layer of the permafrost in Council, Alaska. PsEst3 was successfully overexpressed using a psychrophilic chaperonin co-expression system and was purified by nickel-affinity and size-exclusion chromatography. Recombinant PsEst3 was crystallized at 290 K using the hanging-drop vapour-diffusion method. X-ray diffraction data were collected to 2.1 Å resolution. The crystal was determined to belong to space group P4132 or P4332, with unit-cell parameters a = b = c = 145.33 Å. Further crystallographic analysis needs to be conducted to investigate the structure and function of this esterase.
Crystal structure of 1-[3,5-bis(trifluoromethyl)phenyl]-2-bromoethan-1-one
Authors: Chandrashekharappa Sandeep , Bairagi Keshab M. , Mohan Mahendra K. , Mohanlall Viresh , Kasumbwe Kabange , Venugopala Katharigatta N. , Nayak Susanta K.
Published: May 2018

The title compound, C10H5BrF6O, synthesized via continuous stirring of 3,5-bis(trifluoromethyl) acetophenone with bromine in an acidic medium and concentrated under reduced pressure, crystallizes with four molecules in the unit cell (Z = 4) and one formula unit in the asymmetric unit. In the crystal, molecules are linked in a head-to-tail fashion into dimers along the b-axis direction through weak C—H...Br and C—O...Csp
2 interactions. C—H...O, C—F...π and F...F interactions are also observed.
The crystal structures of 3-O-benzyl-1,2-O-isopropylidene-5-O-methanesulfonyl-6-O-triphenylmethyl-α-D-glucofuranose and its azide displacement product
Authors: Clarke Zane , Barnes Evan , Prichard Kate L. , Mares Laura J. , Clegg Jack K. , McCluskey Adam , Houston Todd A. , Simone Michela I.
Published: May 2018

The effect of different leaving groups on the substitution versus elimination outcomes with C-5 D-glucose derivatives was investigated. The stereochemical configurations of 3-O-benzyl-1,2-O-isopropylidene-5-O-methanesulfonyl-6-O-triphenylmethyl-α-D-glucofuranose, C36H38O8S (3) [systematic name: 1-[(3aR,5R,6S,6aR)-6-benzyloxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-2-(trityloxy)ethyl methanesulfonate], a stable intermediate, and 5-azido-3-O-benzyl-5-deoxy-1,2-O-isopropylidene-6-O-triphenylmethyl-β-L-idofuranose, C35H35N3O5 (4) [systematic name: (3aR,5S,6S,6aR)-5-[1-azido-2-(trityloxy)ethyl]-6-benzyloxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole], a substitution product, were examined and the inversion of configuration for the azido group on C-5 in 4 was confirmed. The absolute structures of the molecules in the crystals of both compounds were confirmed by resonant scattering. In the crystal of 3, neighbouring molecules are linked by C—H...O hydrogen bonds, forming chains along the b-axis direction. The chains are linked by C—H...π interactions, forming layers parallel to the ab plane. In the crystal of 4, molecules are also linked by C—H...O hydrogen bonds, forming this time helices along the a-axis direction. The helices are linked by a number of C—H...π interactions, forming a supramolecular framework.
Crystal structure of 2-{5-[2-(2-hydroxyphenyl)diazen-1-yl]-1-methylpyrrol-2-yl}phenol methanol monosolvate
Authors: Yang Guiwen , Feng Huixiao , Yin Zhenming
Published: May 2018

In the title azopyrrole compound, C17H15N3O2·CH3OH, the azo N=N bond adopts a trans configuration and the pyrrole N and azo group are in an anti orientation. The dihedral angles between the pyrrole ring and the two phenyl rings are 6.7 (3) and 54.7 (3)°. In the crystal, a supramolecular ring structure is formed between two azopyrrole and two methanol solvent molecules through four O—H...O hydrogen bonds.
Explaining and tackling the informal economy: a dual informal labour market approach
Authors: Williams Colin Charles , Bezeredi Slavko
Published: May 2018

Purpose

To transcend the long-standing debate regarding whether workers are driven into the informal economy by either their involuntary “exclusion” or voluntary “exit” from the formal economy, the purpose of this paper is to propose and evaluate the existence of a dual informal labour market composed of an exit-driven “upper tier” and an exclusion-driven “lower-tier” of informal workers, and to explore its policy implications.

Design/methodology/approach

To do so, data are reported from a 2015 survey of the informal economy conducted in South-East Europe involving 6,019 face-to-face interviews in Bulgaria, Croatia and FYR Macedonia.

Findings

Identifying a dual informal labour market with three exit-driven informal workers for every exclusion-driven informal worker, a multinomial logit regression analysis reveals that, compared to the exclusion-driven “lower tier”, the exit-driven “upper tier” is significantly more likely to be populated by the formally employed, retired and those not struggling financially. Participation is not affected by the perceived severity of penalties and likely risks of detection, but relative to those in the exclusion-driven “lower tier”, there is a significant correlation between those doing so for exit rationales and their lack of both horizontal trust and vertical trust in formal institutions.

Practical implications

The outcome is a call to transcend the conventional deterrence approach of increasing the penalties and risks of detection. Instead, to tackle those driven by exit rationales, tackling both the lack of horizontal trust that other citizens are operating in a compliant manner and the lack of vertical trust in formal institutions is advocated. To tackle exclusion-driven informal workers, meanwhile, a focus upon the macro-level economic and social conditions which lead to their participation is required.

Originality/value

This is the first paper to empirically evaluate the existence of a dual informal labour market and to evaluate its policy implications.