bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractNeuropeptides 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

ABSTRACTIn 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

AbstractThe 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.ImportanceBdellovibrioattack 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

SummaryMonitor 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.
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

AbstractCaulobacter 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

SUMMARYHow 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

AbstractIt 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

AbstractThe “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

AbstractMitochondria 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

AbstractIntranasal 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

AbstractThe 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

AbstractThe 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

SummaryThe 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.