bluuebunny/crossref_metadata_2025 huggingface dataset:
The Patchy Distribution of Restriction-Modification System Genes and the Conservation of Orphan Methyltransferases in Halobacteria
Authors: Fullmer Matthew S. , Ouellette Matthew , Louyakis Artemis S. , Papke R. Thane , Gogarten J. Peter
Published: February 2019

Restriction-modification (RM) systems in Bacteria are implicated in multiple biological roles ranging from defense against parasitic genetic elements, to selfish addiction cassettes, and barriers to gene transfer and lineage homogenization. In Bacteria, DNA-methylation without cognate restriction also plays important roles in DNA replication, mismatch repair, protein expression, and in in biasing DNA uptake. Little is known about archaeal RM systems and DNA methylation. To elucidate further understanding for the role of RM systems and DNA methylation in Archaea, we undertook a survey of the presence of RM system genes and related genes, including orphan DNA methylases, in the halophilic archaeal class Halobacteria. Our results reveal that some orphan DNA methyltransferase genes were highly conserved among lineages indicating an important functional constraint, whereas RM systems demonstrated patchy patterns of presence and absence. This irregular distribution is due to frequent horizontal gene transfer and gene loss, a finding suggesting that the evolution and life cycle of RM systems may be best described as that of a selfish genetic element. A putative target motif (CTAG) of one of the orphan methylases was underrepresented in all of the analyzed genomes, whereas another motif (GATC) was overrepresented in most of the haloarchaeal genomes, particularly in those that encoded the cognate orphan methylase.
Phage efficacy in infecting dual-strain biofilms ofPseudomonas aeruginosa
Authors: Testa Samuele , Berger Sarah , Piccardi Philippe , Oechslin Frank , Resch Grégory , Mitri Sara
Published: February 2019

Bacterial viruses, or phage, play a key role in shaping natural microbial communities. Yet much research on bacterial-phage interactions has been conducted in liquid cultures involving single bacterial strains. Critically, phage often have a very narrow host range meaning they can only ever target a subset of strains in a community. Here we explore how strain diversity affects the success of lytic phage in structured communities. In particular, we infect a susceptiblePseudomonas aeruginosastrain PAO1 with lytic phage Pseudomonas 352 in the presence versus absence of an insensitiveP. aeruginosastrain PA14, in liquid culture versus colonies growing on agar. We find that competition between the two bacterial strains reduces the likelihood of the susceptible strain evolving resistance to the phage. This result holds in liquid culture and in colonies. However, while in liquid the phage eliminate the whole sensitive population, colonies contain refuges wherein bacteria can remain sensitive yet escape phage infection. These refuges form mainly due to reduced growth in colony centers. We find little evidence that the presence of the insensitive strain provides any additional protection against phage. Our study reveals that living in a spatially structured population can protect bacteria against phage infection, while the presence of competing strains may instead reduce the likelihood of evolving resistance to phage, if encountered.
A Quasi Birth-and-Death Model For Tumor Recurrence
Authors: Santana Leonardo M. , Ganesan Shridar , Bhanot Gyan
Published: February 2019

A major cause of chemoresistance and recurrence in tumors is the presence of dormant tumor foci that survive chemotherapy and can eventually transition to active growth to regenerate the cancer. In this paper, we propose a Quasi Birth-and-Death (QBD) model for the dynamics of tumor growth and recurrence/remission of the cancer. Starting from a discrete-state master equation that describes the time-dependent transition probabilities between states with different numbers of dormant and active tumor foci, we develop a framework based on a continuum-limit approach to determine the time-dependent probability that an undetectable residual tumor will become large enough to be detectable. We derive an exact formula for the probability of recurrence at large times and show that it displays a phase transition as a function of the ratio of the death rateµAof an active tumor focus to its doubling rateλ. We also derive forward and backward Kolmogorov equations for the transition probability density in the continuum limit and, using a first-passage time formalism, we obtain a drift-diffusion equation for the mean recurrence time and solve it analytically to leading order for a large detectable tumor sizeN.We show that simulations of the discrete-state model agree with the analytical results, except forO(1/N) corrections. Finally, we describe a scheme to fit the model to recurrence-free survival (Kaplan-Meier) curves from clinical cancer data, using ovarian cancer data as an example. Our model has potential applications in predicting how changing chemotherapy schedules may affect disease recurrence rates, especially in cancer types for which no targeted therapy is available.
Imaging of Morphological and Biochemical Hallmarks of Apoptosis with Optimized Optogenetic Actuators
Authors: Godwin Walton C. , Hoffmann George F. , Gray Taylor J. , Hughes Robert M.
Published: February 2019

The creation of pathway-specific optogenetic switches for the activation of cell death pathways can provide insight into the mechanisms of apoptosis and also form a basis for non-invasive, next generation therapeutic strategies. Previous work has employed the Cryptochrome 2 (Cry2)/CIB, a blue light activated protein – protein dimerization module from A. thaliana in conjunction with BAX, an OMM targeting pro-apoptotic protein, for light-mediated initiation of mitochondrial outer membrane permeabilization (MOMP) and downstream apoptosis. In this work, we have further developed our original light activated Cry2-BAX system (henceforth referred to as “OptoBAX”) by improving the photophysical properties and light-independent interaction of our optogenetic switch. The resulting optogenetic constructs have significantly reduced the frequency of light exposure required for the activation of membrane permeabilization, in addition to reducing dark state cytotoxicity. Furthermore, we have utilized OptoBAX in a series of experiments designed to measure the timing of the dramatic morphological and biochemical changes that occur in apoptotic cells following light-induced permeabilization of the outer mitochondrial membrane. Utilizing this data, we construct a timeline of biochemical and morphological events in early apoptosis, in addition to tracking the MOMP-induced redistribution of actin, a protein critical to apoptotic progression.
Drosophilacarboxypeptidase D (SILVER) is a key enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
Authors: Pauls Dennis , Hamarat Yasin , Trufasu Luisa , Schendzielorz Tim M. , Gramlich Gertrud , Kahnt Jörg , Vanselow Jens T. , Schlosser Andreas , Wegener Christian
Published: February 2019

Neuropeptides are processed from larger preproproteins by a dedicated set of enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing enzymes are well characterised in mammals, but little studied outside this group. In contrast to mammals,Drosophilalacks a gene for carboxypeptidase E (CPE), a key enzyme for mammalian peptide processing.

By combining peptidomics and neurogenetics, we addressed the role ofDrosophilacarboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding genesilverin the larva causes lethality, and leads to deficits in adult starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced survival rate and activity levels. A phylogenomic analysis suggests that loss of CPE is not a common insect feature, but specifically occured in Hymenoptera and Diptera. Our results show that dCPD is a key enzyme for neuropeptide processing inDrosophila, and is required for proper peptide-regulated behaviour. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. Our results raise the question whyDrosophilaand other Diptera and Hymenoptera –unlike other insects-have obviously lost the gene for CPE but kept a gene encoding CPD.
Comparison of classification methods for tissue outcome after ischemic stroke
Authors: Tozlu Ceren , Ozenne Brice , Cho Tae-Hee , Nighoghossian Norbert , Mikkelsen Irene Klærke , Derex Laurent , Hermier Marc , Pedraza Salvador , Fiehler Jens , Østergaard Leif , Berthezène Yves , Baron Jean-Claude , Maucort-Boulch Delphine
Published: February 2019

In acute ischemic stroke, identifying brain tissue at high risk of infarction is important for clinical decision-making. This tissue may be identified with suitable classification methods from magnetic resonance imaging (MRI) data. The aim of the present study was to assess comparatively the performance of five popular classification methods (Adaptive Boosting (ADA), Logistic Regression (LR), Artificial Neural Networks (ANN), Random Forest (RF), and Support Vector Machine (SVM)) in identifying tissue at high risk of infarction on human voxel-based brain imaging data. The classification methods were used with eight MRI parameters including diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) obtained in 55 patients. Sensitivity, specificity, the area under the receiver operating curve (ROC) as well as the area under the precision-recall curve criteria were used to compare the method performances. The methods performed equally in terms of sensitivity and specificity while the results of the area under the ROC were significantly better for ADA, LR, ANN and RF. However, there was no statistically significant difference between the performances of these five classification methods regarding the area under the precision-recall curve, which was the main comparison metric.
Variation in genome content and predatory phenotypes betweenBdellovibriosp. NC01 isolated from soil andB. bacteriovorustype strain HD100
Authors: Williams Laura E. , Cullen Nicole , DeGiorgis Joseph A. , Martinez Karla J. , Mellone Justina , Oser Molly
Published: February 2019

The range of naturally occurring variation in the ability ofBdellovibriostrains to attack and kill Gram-negative bacteria is not well understood. Defining phenotypic and associated genotypic variation amongBdellovibriowill clarify how divergent lineages within this genus impact microbial communities and will inform development of predatory bacteria as biocontrol agents to combat bacterial infections. We isolatedBdellovibriosp. NC01 from soil and compared its genome and predatory phenotypes toB. bacteriovorustype strain HD100. Based on analysis of 16S rRNA gene sequences and average amino acid identity, NC01 belongs to a different species than HD100. Genome-wide comparisons and individual gene analyses indicated that eight NC01 genome regions were likely acquired by horizontal gene transfer (HGT), further supporting an important role for HGT inBdellovibriogenome evolution. Within these regions, multiple protein-coding sequences were assigned predicted functions related to transcriptional regulation and transport; however, most were annotated as hypothetical proteins. Compared to HD100, NC01 has a limited prey range and killsE. coliML35 less efficiently. Whereas HD100 drastically reduces the ML35 population and then maintains low prey population density, NC01 causes a smaller reduction in ML35, after which the prey population recovers, accompanied by a decrease in NC01. In addition, NC01 forms turbid plaques on lawns of ML35, in contrast to clear plaques formed by HD100. Characterizing variation in interactions betweenBdellovibrioand Gram-negative bacteria, such as observed with NC01 and HD100, is important for understanding the ecological significance of predatory bacteria and evaluating their effectiveness in clinical applications.

Importance

Bdellovibrioattack and kill Gram-negative bacteria; however, not allBdellovibriostrains are equally efficient at killing the same Gram-negative bacteria. Defining howBdellovibriovary in predatory phenotypes and how this phenotypic variation relates to differences in genotype is important for understanding the ecological significance of predatory bacteria and evaluating their effectiveness in biocontrol of bacterial infections. We determined variation in genome content and predatory phenotypes, including prey range and predation efficiency, betweenBdellovibriosp. NC01 isolated from soil andB. bacteriovorustype strain HD100. NC01 is phylogenetically divergent from HD100, with eight regions of unique gene content likely acquired by horizontal gene transfer. Compared to HD100, the prey range of NC01 is limited, and it was less efficient at killing a strain ofE. coli. These differences may have important implications for how each strain impacts microbial communities in different environments and for the effectiveness of each in clinical applications.
A high-resolution, chromosome-assigned Komodo dragon genome reveals adaptations in the cardiovascular, muscular, and chemosensory systems of monitor lizards
Authors: Lind Abigail L. , Lai Yvonne Y.Y. , Mostovoy Yulia , Holloway Alisha K. , Iannucci Alessio , Mak Angel C.Y. , Fondi Marco , Orlandini Valerio , Eckalbar Walter L. , Milan Massimo , Rovatsos Michail , Kichigin Ilya G. , Makunin Alex I. , Pokorná Martina J. , Altmanová Marie , A. Trifonov Vladimir , Schijlen Elio , Kratochvíl Lukáš , Fani Renato , Jessop Tim S. , Patarnello Tomaso , Hicks James W. , Ryder Oliver A. , Mendelson Joseph R. , Ciofi Claudio , Kwok Pui-Yan , Pollard Katherine S. , Bruneau Benoit G.
Published: February 2019

Monitor lizards are unique among ectothermic reptiles in that they have a high aerobic capacity and distinctive cardiovascular physiology which resembles that of endothermic mammals. We have sequenced the genome of the Komodo dragon (Varanus komodoensis), the largest extant monitor lizard, and present a high resolutionde novochromosome-assigned genome assembly forV. komodoensis, generated with a hybrid approach of long-range sequencing and single molecule physical mapping. Comparing the genome ofV. komodoensiswith those of related species showed evidence of positive selection in pathways related to muscle energy metabolism, cardiovascular homeostasis, and thrombosis. We also found species-specific expansions of a chemoreceptor gene family related to pheromone and kairomone sensing inV. komodoensisand several other lizard lineages. Together, these evolutionary signatures of adaptation reveal genetic underpinnings of the unique Komodo sensory, cardiovascular, and muscular systems, and suggest that selective pressure altered thrombosis genes to help Komodo dragons evade the anticoagulant effects of their own saliva. As the only sequenced monitor lizard genome, the Komodo dragon genome is an important resource for understanding the biology of this lineage and of reptiles worldwide.
Structure of the SARS-CoV NSP12 polymerase bound to NSP7 and NSP8 co-factors
Authors: Kirchdoerfer Robert N. , Ward Andrew B.
Published: February 2019

Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (NSP) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV NSP12 polymerase bound to its essential co-factors, NSP7 and NSP8, using single particle cryo-electron microscopy. NSP12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is unexpectedly bound by two NSP8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into NSP12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.
Absolute measurements of mRNA translation inC. crescentusreveal important fitness costs of vitamin B12scavenging
Authors: Aretakis James R. , Gega Alisa , Schrader Jared M.
Published: February 2019

Caulobacter crescentusis a model for the bacterial cell cycle which culminates in asymmetric cell division, yet little is known about the absolute levels of protein synthesis of the cellular parts needed to complete the cell cycle. Here we utilize ribosome profiling to provide absolute measurements of mRNA translation of theC. crescentusgenome, providing an important resource for the complete elucidation of the cell cycle gene-regulatory program. Analysis of protein synthesis rates revealed ∼4.5% of cellular protein synthesis are for genes related to vitamin B12import (btuB) and B12independent methionine biosynthesis (metE) when grown in common growth media lacking B12. While its facultative B12lifestyle provides a fitness advantage in the absence of B12, we find that it provides lower fitness of the cells in the presence of B12, potentially explaining why manyCaulobacterspecies have lost themetEgene and become obligates for B12.
Mesoscale cortical dynamics reflect the interaction of sensory evidence and temporal expectation during perceptual decision-making
Authors: Orsolic Ivana , Rio Maxime , Mrsic-Flogel Thomas D. , Znamenskiy Petr
Published: February 2019

How sensory evidence is transformed across multiple brain regions to influence behavior remains poorly understood. We trained mice in a visual change detection task designed to separate the covert antecedents of choices from activity associated with their execution. Widefield calcium imaging across dorsal cortex revealed fundamentally different dynamics of activity underlying these processes. While signals related to execution of choice were widespread, fluctuations in sensory evidence in the absence of overt motor responses triggered a confined activity cascade, beginning with transient modulation of visual cortex, followed by sustained recruitment of secondary and primary motor cortex. The activation of motor cortex by sensory evidence was selectively gated by animals’ expectation of when the stimulus was likely to change. These results identify distinct activation profiles of specific cortical areas during decision-making, and show that the recruitment of motor cortex depends on the interaction of sensory evidence and expectation.
Genetic variation in the odorant receptor gene OR4 and bit habits in natural populations of Aedes aegypti from Antioquia department, Colombia
Authors: Pino Juan Sebastian
Published: February 2019

It has been determined factors that make humans more attractive to mosquitoes and which strategies they use to detect a potential host. Preferential differences for human/non-human hosts are related to variations in odorant receptors (OR) genes in the Aedes aegypti mosquitoes. This study use sequencing to establish the genetic variation in the odor receptor OR4 in 900 mosquitoes from different regions of Antioquia. A behavioral test using an olfactometer was also made to stablish the relationship of these variation with the attraction on different human hosts. The analysis in the attraction and OR4 variants did not show significant differences in the arrival rate among different human hosts. No significant differences in the description of OR4 variants between populations and between hosts, show that this gene is homogeneously distributed. The analysis showed a high genetic population diversity, measured as polymorphism and heterozygosity. This may be due to a few high frequency haplotypes in all the populations examined, suggesting a model of high gene flow between populations and/or selection in favor of these variants in all populations. Other low-frequency variants, many of which are population-specific, reflect the effect of genetic drift probably due to stochastic changes in the size of natural mosquito populations.
Adaptation and latitudinal gradients in species interactions: nest predation in birds
Authors: Freeman Benjamin G. , Scholer Micah N. , Boehm Mannfred M. A. , Heavyside Julian , Schluter Dolph
Published: February 2019

The “biotic interactions” hypothesis—that stronger interspecific interactions in the tropics drive faster evolution and speciation, giving rise to the latitudinal diversity gradient—has inspired many tests of whether certain biotic interactions are indeed stronger in the tropics. However, the possibility that populations have adapted to latitudinal differences in species interactions, blunting effects on evolutionary rates, has been largely ignored. Here we show that mean rates of nest predation experienced by land birds vary minimally with latitude in the Western Hemisphere. This result is surprising because nest predation in birds is a canonical example of a strong tropical biotic interaction. We explain our finding by demonstrating that (1) rates of nest predation are in fact higher in the tropics, but only when controlling for the length of the nesting period, (2) long nesting periods are associated with reduced predation rates, and (3) tropical birds have evolved particularly long nesting periods. We suggest this is a case example of how adaptation to a biotic interaction can alter observed latitudinal gradients in interaction strength, potentially equalizing evolutionary rates among latitudes. More broadly, we advocate for tests of the biotic interactions hypothesis to consider both latitudinal patterns in interaction strength and evolutionary responses to these interactions.
Clueless forms dynamic, insulin-responsive bliss particles sensitive to stress
Authors: Sheard K. M. , Thibault-Sennett S. A. , Sen A. , Shewmaker F. , Cox R. T.
Published: February 2019

Mitochondria perform a myriad of biochemical functions in the cell that integrate ATP production and metabolism. While mitochondria contain their own genome, mtDNA, it only encodes thirteen proteins required for oxidative phosphorylation, thus well over one thousand proteins required for all mitochondrial functions are encoded in the nucleus. One such protein is Drosophila Clueless (Clu), whose vertebrate homolog is Clustered mitochondria homolog (Cluh). Clu/Cluh is a ribonucleoprotein that regulates mRNAs destined for import into mitochondria and is an essential protein that regulates cellular metabolism. Clu forms large particles in the cytoplasm, although how these particles relate to nutrition and metabolic stress is unknown. Using live-imaging, we show Clu particles are highly dynamic. Clu particles appear to be unique as they do not colocalize with many known cytoplasmic bodies. In addition, Clu particle formation is highly dependent on diet as ovaries from starved females no longer contain Clu particles although Clu protein levels remain the same and insulin is necessary and sufficient for Clu particle formation. Oxidative stress also disperses particle. Since Clu particles are only present under optimal conditions we are naming them bliss particles. These observations identify Clu particles as unique, stress-sensitive cytoplasmic ribonucleoprotein particles whose absence corresponds with altered mitochondrial function and localization.
Oxytocin modulation of self-other distinction is replicable and influenced by oxytocin receptor (OXTR) genotype
Authors: Zhao Weihua , Luo Ruixue , Sindermann Cornelia , Li Jialin , Wei Zhenyu , Zhang Yingying , Liu Congcong , Le Jiao , Quintana Daniel S. , Montag Christian , Becker Benjamin , Kendrick Keith M
Published: February 2019

Intranasal oxytocin (OXT) has been associated with effects on diverse social-emotional domains in humans, however progress in the field is currently hampered by poor replicability. Limited statistical power and individual differences in biological factors, such as oxytocin receptor (OXTR) genetics, may have contributed to these variable findings. To this end, we present a pharmaco-genetic study aiming at (1) replicating previous findings suggesting that intranasal oxytocin (24 IU) blurs self-other distinction in a large sample of n = 170 male subjects, (2) determining whether variations in common receptor polymorphisms (rs237887, rs2268491, rs2254298, rs53576, rs2268498) influence sensitivity to oxytocin’s behavioral effects. Employing a validated oxytocin-sensitive trait judgment paradigm, we confirmed that it blurred self-other distinction in terms of decision time and subsequent memory. However, oxytocin only influenced decision time in rs53576 G carriers, whereas effects on memory performance were most pronounced in rs2268498 TT homozygotes. In summary, the current study replicates our previous findings showing that oxytocin blurs self-other distinction and suggests that sensitivity to its effects in this domain are receptor genotype dependent.
Visualizing Conformation Transitions of the Lipid Flippase MurJ
Authors: Kuk Alvin C. Y. , Hao Aili , Guan Ziqiang , Lee Seok-Yong
Published: February 2019

The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases. MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials. However, the flipping mechanism of LLOs including Lipid II remains poorly understood due to a dearth of structural information. Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations. Together with cysteine accessibility, mass spectrometry, and complementation studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identified the key ion for function, and provide a framework for the development of inhibitors.
Metagenomic analysis reveals large potential for carbon, nitrogen and sulfur cycling in coastal methanic sediments of the Bothnian Sea
Authors: Rasigraf Olivia , van Helmond Niels A.G.M. , Frank Jeroen , Lenstra Wytze K. , Egger Matthias , Slomp Caroline P. , Jetten Mike S.M.
Published: February 2019

The Bothnian Sea is an oligotrophic brackish basin characterized by low salinity and high concentrations of reactive iron, methane and ammonium in the sediments potentially enabling an intricate microbial network. Therefore, we analyzed and compared biogeochemical and microbial profiles at one offshore and two near coastal sites in the Bothnian Sea. 16S rRNA amplicon sequence analysis revealed stratification of both bacterial and archaeal taxa in accordance with the geochemical gradients of iron, sulfate and methane. The communities at the two near coastal sites were more similar to each other than that at the offshore site located at a greater water depth. To obtain insights into the metabolic networks within the iron-rich methanic sediment layer located below the sulfate-methane transition zone (SMTZ), we performed metagenomic sequencing of sediment-derived DNA. Genome bins retrieved from the most abundant bacterial and archaeal community members revealed a broad potential for respiratory sulfur metabolism via partially reduced sulfur species. Nitrogen cycling was dominated by reductive processes via a truncated denitrification pathway encoded exclusively by bacterial lineages. Gene-centric fermentative metabolism analysis indicated the central role of acetate, formate, alcohols and hydrogen in the analyzed anaerobic sediment. Methanogenic/-trophic pathways were dominated by Methanosaetaceae, Methanosarcinaceae, Methanomassiliicoccaceae, Methanoregulaceae and ANME-2 archaea. Thorarchaeota and Bathyarchaeota encoded pathways for acetogenesis. Our results indicate flexible metabolic capabilities of core community bacterial and archaeal taxa, which can adapt to changing redox conditions, and with a spatial distribution in Bothnian Sea sediments that is likely governed by the quality of available organic substrates.
Robo2 regulates synaptic oxytocin content by affecting actin state
Authors: Anbalagan Savani , Blechman Janna , Gliksberg Michael , Rotkopf Ron , Dadosh Tali , Levkowitz Gil
Published: February 2019

The regulation of neuropeptide level at the site of release is essential for proper neurophysiological functions. We focused on a prominent neuropeptide, oxytocin (OXT), and used the zebrafish as anin vivomodel to visualize and quantify OXT content at the resolution of a single synapse. We found that OXT-loaded synapses were surrounded by polymerized actin. Perturbation of actin filaments by cytochalasin-D resulted in decreased synaptic OXT levels. Live imaging of the actin probe, Lifeact-EGFP, showed reduced mobility in OXT synapses inrobo2mutants, which displayed decreased synaptic OXT content. Using a novel transgenic reporter line allowing real-time monitoring of OXT-loaded vesicles, we showed thatrobo2mutants display slower rate of vesicles accumulation. OXT-specific expression of dominant-negative Cdc42, which is a key regulator of actin dynamics and a downstream effector of Robo2, led to a dose-dependent increase in OXT content in WT, and a dampened effect inrobo2mutants. Our results link Robo2-Cdc42 signalling, which controls local actin dynamics, with the maintenance of synaptic neuropeptide levels.
H2A.Z-dependent and -independent recruitment of metabolic enzymes to chromatin required for histone modifications
Authors: Choi Sujung , Jeon Yong Heui , Yang Zhi , He Minzhen , Shin Hyewon , Pfleger Jessica , Sayed Danish , Astrof Sophie , Abdellatif Maha
Published: February 2019

H2A.Z plays a fundamental role in the regulation of transcription and epigenetics, however, the mechanisms that underlie its functions are not fully understood. Using rapid chromatin immunoprecipitation-mass spectrometry, we uncovered the association of H2A.Z-bound chromatin with an array of tricarboxylic acid cycle and beta-oxidation enzymes in the mouse heart. Recombinant green florescence fusion proteins combined with mutations of putative nuclear localization signals of select enzymes, including acetyl-CoA acyltransferase 2 (ACAA2), oxoglutarate dehydrogenase (OGDH), and isocitrate dehydrogenase 2 confirmed their nuclear localization and chromatin binding in both rodent and human cells. Conclusively, chromatin immunoprecipitation-deep sequencing, confirmed the selective association of ACAA2 and OGDH with H2A.Z-occupied transcription start sites. Finally, human H2A.Z-deficient HAP1 cells exhibited reduced chromatin-bound metabolic enzymes, with the exception of pyruvate dehydrogenase, accompanied with reduced posttranslational histone modifications. Thus, the data show that metabolic enzymes are recruited to active promoters for potential site-directed epigenetic modifications.
Metabolic basis of brain-like electrical signalling in bacterial communities
Authors: Martinez-Corral Rosa , Liu Jintao , Prindle Arthur , Süel Gürol M. , Garcia-Ojalvo Jordi
Published: February 2019

Information processing in the mammalian brain relies on a careful regulation of the mem-brane potential dynamics of its constituent neurons, which propagates across the neuronal tissue via electrical signalling. We recently reported the existence of electrical signalling in a much simpler organism, the bacterium Bacillus subtilis. In dense bacterial communi-ties known as biofilms, nutrient-deprived B. subtilis cells in the interior of the colony use electrical communication to transmit stress signals to the periphery, which interfere with the growth of peripheral cells and reduce nutrient consumption, thereby relieving stress from the interior. Here we explicitly address the interplay between metabolism and elec-trophysiology in bacterial biofilms, by introducing a spatially-extended mathematical model that combines the metabolic and electrical components of the phenomenon in a discretised reaction-diffusion scheme. The model is experimentally validated by environmental and ge-netic perturbations, and confirms that metabolic stress is transmitted through the bacterial population via a potassium wave. Interestingly, this behaviour is reminiscent of cortical spreading depression in the brain, characterised by a wave of electrical activity mediated by potassium diffusion that has been linked to various neurological disorders, calling for future studies on the evolutionary link between the two phenomena.
Hospital use of antibiotics as the main driver of infections with antibiotic-resistant bacteria – a reanalysis of recent data from the European Union
Authors: Fischer Matthias M. , Bild Matthias
Published: February 2019

Antimicrobial resistance in bacteria causes significant morbidity worldwide. The development and acquisition of resistance to antibiotics is believed to primarily develop under the selective pressure of widespread antibiotic use in humans, however antimicrobial usage in livestock has been proposed as additional, if not principal, driver of antibiotic resistance. In this work, we correlate recent data from the European Union on antibiotic resistance rates with data on antibiotic usage in the primary care and hospital sector and data on veterinary antimicrobial consumption across the individual member states. We quantify the strength of these different potential drivers of antimicrobial resistance in order to compare their biological importance. We found that the correlation between antibiotic use in the hospital sector and antibiotic resistance rates is significantly higher than the correlation between resistance rates and any of the other two predictors. This suggests increased antibiotic use in hospitals as the main driver of the development of antibiotic resistances and necessitates further research on and a re-evaluation of the risks associated with antibiotic use in human and veterinary medicine.
Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)
Authors: Lee Laura , Seager Richard , Wilkinson Kevin A. , Henley Jeremy M.
Published: February 2019

The mitochondrial outer membrane protein Mitochondrial Fission Factor (Mff) plays a key role in both physiological and pathological fission. It is well established that in stressed or functionally impaired mitochondria the PINK1 recruits the ubiquitin ligase Parkin which ubiquitinates Mff to facilitate the removal of defective mitochondria and maintain the integrity mitochondrial network. Here we show that, in addition to this clearance pathway, Parkin also ubiquitinates Mff in a PINK1-dependent manner under basal, non-stressed conditions to regulate constitutive Mff turnover. We further show that removing Parkin with shRNA knockdown does not completely prevent Mff ubiquitination under these conditions indicating that at least one other ubiquitin ligase contributes to Mff proteostasis. These data demonstrate that Parkin plays a role in physiological maintenance of mitochondrial membrane protein composition in healthy mitochondria through constitutive low-level activation.
Application of seaweed organic components increases tolerance to Fe deficiency in tomato plants
Authors: Carrasco-Gil Sandra , Allende-Montalbán Raúl , Hernández-Apaolaza Lourdes , Lucena Juan José
Published: February 2019

The beneficial effects of seaweed extracts have been related to plant growth regulators present in seaweeds. However, algae extracts comprise other organic compounds such as phenols, mannitol, alginates, laminarins and fucoidans that may have a relevant role regarding abiotic stress tolerance due to Fe deficiency. Therefore, we evaluated the individual effect of these organic compounds on the mitigation of Fe deficiency applying a range of concentrations (x1/10, x1, x10) in agar Petri dishes (in tomato seeds) and in the nutrient solution of a hydroponic system (tomato plants). Germination and plant growth promotion, root morphology, chlorophyll content and antioxidant activity were determined. Results showed that the lowest concentration x1/10 and phenolics, laminarin and fucose compounds contributed to increase the tolerance to Fe deficiency in tomato plants.
Future sea-level rise drives rocky intertidal habitat loss and benthic community change
Authors: Kaplanis Nikolas J. , Edwards Clinton B. , Eynaud Yoan , Smith Jennifer E.
Published: February 2019

Rocky intertidal ecosystems may be particularly susceptible to sea-level rise impacts but few studies have explored community scale response to future sea-level scenarios. Combining remote-sensing with large-area imaging, we quantify habitat extent and describe biological community structure at two rocky intertidal study locations in California. We then estimate changes in habitat area and community composition under a range of sea-level rise scenarios using a model-based approach. Our results suggest that future sea-level rise will significantly reduce rocky intertidal area at our study locations, leading to an overall decrease in benthic habitat and a reduction in overall invertebrate abundances, but increased densities of certain taxa. These results suggest that sea-level rise may fundamentally alter the structure and function of rocky intertidal systems. As large scale environmental changes such as sea-level rise accelerate in the next century, more extensive spatially-explicit monitoring at ecologically relevant scales will be needed to visualize and quantify the impacts to biological systems.
Serologic evidence of seasonal influenza A and B viruses in HIV patients on combined antiretroviral therapy in Lagos, Nigeria
Authors: Anjorin AbdulAzeez A. , Adepoju Barakat A.
Published: February 2019

We investigated serologic evidence of seasonal influenza A and B, and the possibility of their co-infection in HIV patients on combined antiretroviral therapy (cART) in Lagos, Nigeria. A prospective cross-sectional study was designed. A total of 174 HIV positive patients were bled by venipuncture after filling structured questionnaire at the APIN-LUTH clinic, from August to September, 2018. Clear sera were analysed for the detection and quantitative determination of immunoglobulin M specific antibodies to seasonal influenza A subtypes-H1N1 and H3N2, and influenza B by Enzyme Immunoassay (Demeditec, Germany). Results were analysed with Chi-square at 95 % confidence interval. Demographic characteristics showed median age of 44 (mean 45.1, mode 40, range: 18-74) years. Out of the 174 HIV positive patients, 39.7 % (69/174) were seropositive for influenza A and/or B viruses with 58/69 (84.1 %) being positive for influenza A, 11/69 (16 %) for influenza B, and 9/69 (13.4 %) co-infection of influenza A and B. Of the 69 influenza-seropositive patients, age group 41‒ 50 had the highest seroprevalence of 39.1 % (27/69). Females recorded the highest seropositivity of 65.2 % (45/69). Eighty eight (88) % (61/ 69) were on fixed dose cART while 74 % (51/69) were virologically suppressed with HIV RNA < 400 copies/ml. In addition, 2/69 (2.9 %) were positive for HbsAg. Out of the 19/69 (27.5 %) immunocompromised patients (CD4 < 400 cells/mm3), 4/19 (21.1 %) were severely immunosuppressed (CD4 < 200 cells/mm3). This study revealed serologic evidence of recent circulation of wild influenza A and B viruses in highly suppressed HIV RNA patients on cART. Nonetheless, co-infection with HbsAg and immunocompromised state may further predispose them to serious influenza life threatening complications. Strong advocacy on the need to reduce risk of exposure to influenza, and provision of influenza vaccine in Nigeria are recommended to prevent such complications.
Genetic basis of plasticity for forage quality traits in response to water deficit in a diverse germplasm panel of alfalfa
Authors: Yu Long-Xi , Boge Bill , Hu Jinguo , Fransen Steven , Norberg Steven
Published: February 2019

Plant phenotypic plasticity is the ability of plants to express different phenotypes in response to environmental variations. Genetic bases by which phenotypic plasticity affects plant adaptation to environmental change remain largely unknown. In the present study, we characterized 26 forage quality traits in a panel of alfalfa 198 accessions in a field trial under water deficit gradient. The regression analysis revealed that the values of fiber-related traits decreased, while those among energy-related traits increased, as water deficit increased. Genetic loci for forage quality traits were investigated by Genome-wide association studies (GWAS) under different levels of water deficit. Genetic loci associated with forage quality traits were identified and compared. Similar regions were found between energy-related traits when grand means were used for GWAS. Most of the associated markers were identified under water deficit, suggesting genetic mechanisms for forage quality traits were differ between well-watered and water stressed plants. Although GWAS on forage quality have been reported, we are the first to address the genetic factors for forage quality traits under water deficit in autotetraploid alfalfa. The information gained from the present study will be useful for the genetic improvement of alfalfa with enhanced drought/salt tolerance while maintaining forage quality.
Differences in conventional and seniors-oriented apartment management
Authors: Ewen Heidi H. , Carswell Andrew
Published: February 2019

Purpose

From the consumer side, this paper aims to highlight some of the various characteristics that older renters seek out from their apartment buildings, relative to conventional multifamily residential buildings and, from the operational side, to examine some of the costs involved in daily operation of such buildings.

Design/methodology/approach

The Rental Housing Finance Survey provides data that enables scholars to test empirical differences in amenities and costs between senior-oriented communities and other apartment buildings.

Findings

Occupancy rates outpace the rate for all other apartment communities. Regarding amenities, senior apartment communities are more likely than other communities to have a fitness center on premises, but less likely to have a swimming pool. Market value for senior properties is usually less than properties marketed toward multi-family property tenants. This difference may be due to a higher pattern of both operating/capital expenses within senior communities. Part of these increases in operating costs is due to a higher propensity to hire professional management companies and a higher fee for managing senior apartment communities.

Originality/value

Literature on seniors living within apartment communities is somewhat sparse, particularly regarding the operational aspects of managing apartment communities. There is a dearth of information on industry success measurements known as operating and capital expenditures. This study triangulates multiple sources of data to investigate differences in cost of senior housing apartment communities, as well as amenity structures.
Technology in problem-based learning: helpful or hindrance?
Authors: Fukuzawa Sherry , Cahn Joel
Published: February 2019

Purpose

The purpose of this paper is to examine the relationship between student motivation and technology in the implementation of problem-based learning (PBL) in a technologically enhanced active learning classroom (ALC).

Design/methodology/approach

PBL was implemented in an undergraduate course in human osteology (n=49) at a large Canadian University. Numerous activities using the ALC technology were conducted to engage students in self-directed active learning. Students wrote critical self-reflections at the beginning of the course and with each PBL report. They completed a survey at the end of the course using a Likert scale that included written comments on their motivation toward different uses of technology.

Findings

Students generally had high motivation toward PBL at the end of the course. Their evaluation of the technology to support PBL was dependent on the activity. Students (88 percent) appreciated the use of an overhead camera to visualize anatomical elements, and short problem-solving exercises using the whiteboard but they negatively evaluated the real-time projection of PBL sessions through a discussion board (52 percent). Almost half of the class (43 percent) felt that technology was a hindrance to their learning process in PBL.

Originality/value

This study demonstrates the complex relationship between student motivation toward active learning, the learning environment, and technology. Instructors and students influence the learning environment through their conceptions of effective teaching. According to this framework, technology should be implemented not only according to the teaching method, but consider teaching conceptions and the learning environment.
Connecting the silos
Authors: Rasmussen Pennington Diane , Cagnazzo Laura
Published: February 2019

Purpose

The purpose of this paper is to determine how information professionals in Scotland and in European national libraries perceive linked data (LD) as well as if and how they are implementing it.

Design/methodology/approach

The authors applied four data collection techniques: a literature review, semi-structured interviews (n=15), online resources analysis (n=26) and an online survey (n=113). They used constant comparative analysis to identify perceived benefits and challenges of LD implementation, reasons behind adoption or non-adoption of LD and the issues hindering its implementation in libraries.

Findings

Some projects demonstrate LD’s potential to augment the visibility and discoverability of library data, alongside with overcoming linguistic barriers, and supporting interoperability. However, a strong need remains to demonstrate the Semantic Web’s potential within libraries. Participants identified lack of expertise and lack of resources/time/staff as implementation barriers. Several other issues remain unsolved, such as licensing constraints, as well as difficulties with obtaining management buy-in for LD initiatives, even where open data are government-mandated.

Practical implications

Information professionals and vendors should collaborate to develop tools for implementation. Advocacy through disseminating and reviewing successful implementations can help to solve practical difficulties and to obtain management buy-in.

Originality/value

This is the first known study to present a multinational, comprehensive picture of library LD implementations and associated librarians’ perceptions of LD.