bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host_microbe_PPI - R package to analyse intra-species and inter-species protein-protein interactions in the model plant Arabidopsis thaliana
Authors: Nussbaumer Thomas 
Published: February 2019

AbstractIntra-species protein-protein interactions (PPI) provide valuable information about the systemic response of a model species when facing either abiotic and biotic stress conditions. Inter-species PPI can otherwise offer insights into how microbes interact with its host and can provide clues how early infection mechanism takes place. To understand these processes in a more comprehensive way and to compare it with experimental outcomes from omics studies, we require additional methods to analyse and visualize PPI data. We demonstrate the user-interface host_microbe_PPI that is implemented in R Shiny. It allows for interactively analysing inter-species and intra-species datasets from various published Arabidopsis thaliana datasets. It enables among other features comparisons of the centrality measurements (degree, betweenness and closeness) and analysis the existence of orthologous proteins in closely related genomes, e.g. when gene loss in host and non-host plants is compared. Arabidopsis was used even so the tool can be also applied in other host-microbe systems.
Associations between depth and micro-diversity within marine viral communities revealed through metagenomics
Authors: Coutinho FH , Rosselli R , Rodríguez-Valera F 
Published: February 2019

AbstractViruses are extremely abundant and diverse biological entities that contribute to the functioning of marine ecosystems. Despite their recognized importance no studies have addressed trends of micro-diversity in marine viral communities across depth gradients. To fill this gap we obtained metagenomes from both the cellular and viral fractions of Mediterranean seawater samples spanning the epipelagic to the bathypelagic zone at 15, 45, 60 and 2000 meters deep. The majority of viral genomic sequences obtained were derived from bacteriophages of the order Caudovirales, and putative host assignments suggested that they infect some of the most abundant bacteria in marine ecosystems such as Pelagibacter, Puniceispirillum and Prochlorococcus. We evaluated micro-diversity patterns by measuring the accumulation of synonymous and non-synonymous mutations in viral genes. Our results demonstrated that the degree of micro-diversity differs among genes encoding metabolic, structural, and replication proteins and that the degree of micro-diversity increased with depth. These trends of micro-diversity were linked to the changes in environmental conditions observed throughout the depth gradient, such as energy availability, host densities and proportion of actively replicating viruses. These observations allowed us to generate hypotheses regarding the selective pressures acting upon marine viruses from the epipelagic to the bathypelagic zones.
Cold Vacuum Extracts of Double Cherry Blossom (Gosen-Sakura) Leaves Show Antitumor Activity
Authors: Shibato Junko , Takenoya Fumiko , Hirabayashi Takahiro , Kimura Ai , Iwasaki Yusuke , Toyota Yoko , Hori Motohide , Tamogami Shigeru , Rakwal Randeep , Shioda Seiji 
Published: February 2019

AbstractThe present research examines the possibility of finding bio-molecular compounds from the double cherry blossom (termed as ‘Gosen-Sakura’ of Gosen-city, Niigata-prefecture, Japan) leaves, which have been long used in the preparation of the traditional Japanese sweet (wagashi) – ‘sakura-mochi’. Based on its indicated anti-microbial properties historically, our study provides a new low temperature vacuum extraction method for extracting ‘near natural form of water soluble leaf (cell) extracts from the Gosen-Sakura, and demonstrates the presence of some ‘novel’ compound(s) with anti-tumor cell lines proliferation inhibitory affects through the MTT assay. To our knowledge, no reports exist on the sakura tree ‘leaf (cell) extracts’ inhibiting tumor cell line growth. We further examined and compared the effects of known compounds with anti-tumor activity, coumarin and benzyl alcohol with Gosen-Sakura leaf extract; results lead us to hypothesize that the Gosen-Sakura leaf extract contains substance(s) other than the above 2 known compounds, with antitumor effect. Additionally, we speculate on the underlying mechanism of action of the Gosen-Sakura leaf extract by targeting cell division at the point of DNA synthesis and causing apoptosis. In conclusion, we present scientific evidence on the presence of a certain ‘novel’ biomolecule(s), with anti-tumor activity, in the Gosen-Sakura leaf which has been long used as a Japanese – the ‘sakura-mochi’.
Analysis of immunological resistance to primary Mycobacterium tuberculosis infection in humans
Authors: Weiner January , Domaszewska Teresa , Donkor Simon , Hill Philip C. , Sutherland Jayne S. 
Published: February 2019

AbstractBackgroundDespite recent advances in diagnosis and treatment, tuberculosis (TB) remains a major infectious disease killer in resource-poor settings. Strategies to prevent Mycobacterium tuberculosis (Mtb) infection are urgently required. By characterising natural protective immunity to Mtb infection we aimed to identify correlates of protection to guide vaccine development and other immune based therapies.MethodsTwo groups of Mtb-exposed contacts of TB patients were recruited in The Gambia and assessed for Mtb infection status using either tuberculin skin test (TST) reactivity at baseline and 3 months or QuantiFERON (QFT) reactivity at baseline and 6 months. For both groups, converters were defined as having a negative test at baseline and a positive one at follow-up, while those with a negative test at both time-points were defined as non-converters (Mtb resisters). Participants were analysed using RNA-sequencing and plasma Mtb proteome IgA and IgG arrays.ResultsSeveral genes were found to be differentially expressed at baseline between the groups prior to any signs of infection by current tests. Modular analysis revealed a distinct B cell gene signature in TST non-converters compared to converters (at q < 10-6, AUC > 0.7), which was only present in the most highly exposed group. Interestingly, when infection status was defined by QFT, enrichment of Type I IFN and antiviral gene signatures was observed. Plasma IgG and IgA antibody reactivity across the entire Mtb proteome showed the best differentiation in individuals with the highest exposure. An AUC of 1.0 (q<10-3) was observed for IgA reactivity to Rv0134 and an AUC of 0.98 for IgA reactivity to both Rv0629c and Rv2188c (all lower in TST non-converters). IgG reactivity to Rv3223c resulted in an AUC of 0.96 (q < 10-4) and was again lower in TST non-converters. The highest AUC for those with lower Mtb exposure were 0.84 (Rv2411c) for IgA and 0.83 (Rv2131c) for IgG.ConclusionsThese data provide insight into the early protective response to Mtb infection and possible avenues for novel therapeutic strategies to prevent Mtb infection.
Tuning network dynamics from criticality to the chaotic balanced state
Authors: Li Jingwen , Shew Woodrow L. 
Published: February 2019

AbstractAccording to many experimental observations, neurons in cerebral cortex tend to operate in an asynchronous regime, firing independently of each other. In contrast, many other experimental observations reveal cortical population firing dynamics that are relatively coordinated and occasionally synchronous. These discrepant observations have naturally led to a lively debate surrounding discrepant hypotheses. A commonly hypothesized explanation of asynchronous firing is that excitatory and inhibitory neurons are precisely correlated, nearly canceling each other, resulting in the so-called ‘chaotic balanced state’. On the other hand, the ‘criticality’ hypothesis posits an explanation of the more coordinated state that also requires a certain balance of excitatory and inhibitory interactions. Both hypotheses claim the same qualitative mechanism - properly balanced excitation and inhibition. Thus, a natural question arises: how are the chaotic balanced state and criticality related, how do they differ? Here we propose an answer to this question based on investigation of a simple, network-level computational model. We show that the strength of inhibitory synapses relative to excitatory synapses can be tuned from weak to strong to generate a family of models that spans a continuum from ‘criticality’ to the ‘chaotic balanced state’. Our results bridge two long-standing competing hypotheses and offer a possible explanation of discrepant experimental observations: neuromodulatory mechanisms that tune the strength of excitatory and inhibitory synapses may tune cortical state from criticality to the balanced state, and to intermediate states between these extremes.Author summaryWhat is the dynamical state of cerebral cortex? Are neurons mostly uncorrelated, firing asynchronously with each other? Are synchronous oscillations important? The answers to these questions have fundamental implications for how the cortical neural population encodes and processes information. Here we show that two possible scenarios - criticality and the chaotic balanced state - that are typically considered incompatible can be attained in the same network by maintaining a certain kind of balance, while tuning the strength of inhibition relative to excitation.
PROGRESSION OF AUTOANTIBODIES ANTI-GAD AND ANTI-IA2 IN TYPE 1A DIABETICS AGED OF 5 TO 21 YEARS IN CÔTE D’IVOIRE
Authors: Judith Trébissou Aïssé Florence , Yapo-Crezoit Chiayé Claire Antoinette , Sibailly Pascal , Sanogo Mamadou , Ankotché Amos , Kouassi Dinard , Thérèse Kouassi Marie , Masmoudi Hatem , Yapo Adou Francis 
Published: February 2019

AbstractBackgroundDiabetes autoantibodies are indispensable markers of diabetes classification.Objectiveto research autoantibodies anti-GAD and anti-IA2 in type 1A diabetics (T1D) aged 5 to 21 years, and to follow the progression of these autoantibodies in T1D patients, in Côte d’Ivoire.MethodsThe study population composed of 28 T1D patients, aged 5 to 21 years. T1D were followed up in two diabetes care centers in Abidjan district, Endocrinology departments of U.H.C of Yopougon and Treichville. Anti-GAD and anti-IA2 autoantibodies were researched by ELISA.Resultsanti-GAD and anti-IA2 were present in T1D and their siblings. After 2 years of diabetes, the titer of the anti-GAD autoantibodies increased to the mean value of 677.10 ± 353.20 IU / ml. Then, a fall of the anti-GAD autoantibodies until the cancellation was observed from the 8th to the 9th with values of 117 IU / ml to 10.14 IU / ml. Anti-IA2 autoantibodies fall at 9th year of diabetes with a value of 55.10 IU / ml.Conclusionanti-GAD and anti-IA2 autoantibodies persist after 9 years of diabetes, causing total destruction over time of the pancreatic β-cell mass in patients from Côte d’Ivoire, leading them to the death.
The value of non-motor features and genetic variants of Parkinson’s disease for clustering Lewy body diseases
Authors: Lucas-Jiménez Olaia , Diez Ibai , Ojeda Natalia , Ibarretxe-Bilbao Naroa , Peña Javier , Tijero Beatriz , Galdós Marta , Murueta-Goyena Ane , Pino Rocío Del , Acera Marian , Gómez-Esteban Juan Carlos , Gabilondo Iñigo 
Published: February 2019

ABSTRACTIntroductionThe use of non-motor Parkinson’s disease (PD) features and genetic PD variants for clustering analyses may refine the phenotypic classification of idiopathic Lewy body (LB) diseases.MethodsOne-hundred participants [n=7 E46K-SNCA (n=5 symptomatic and n=2 asymptomatic), n=4 PARK2, n=3 LRRK2, n=8 dementia with Lewy bodies (DLB), n=48 idiopathic PD (iPD), n=30 healthy controls (HC)] underwent a comprehensive evaluation of non-motor and motor PD features. Non-motor features were used to perform a hierarchical clustering analysis with patients and HC using a Scikit-learn toolkit.ResultsClustering analysis suggested three clusters of subjects including Cluster 1 or “Normal-to-mild”: young iPD (< 60 years) classified together with most HC and the variable LB burden genetic PD variants (PARK2 and LRRK2) characterized by having normal-to-mild cognitive disabilities and mild-to-moderate motor disability with few axial symptoms; Cluster 2 or “Mild-to-moderate”: old iPD patients (>60 years) classified together with the lowest symptomatic E46K-SNCA, PARK2 carriers and HCs, characterizing by having mild-to-moderate cognitive and motor disabilities with few axial symptoms; and Cluster 3 or “Severe”: old iPD (>60 years) classified together with all DLB and the most symptomatic E46K-SNCA carriers, characterized by having severe pattern-specific cognitive disabilities (visual attention, perception, processing speed, memory and executive functions) and severe motor PD manifestations with marked axial symptoms.ConclusionsOur study supports the potential value of incorporating genetic PD variants in data-driven iPD classification algorithms and the usefulness of non-motor PD features, especially visual cognition abnormalities, to facilitate the identification of aggressive LB diseases.
Honey bees, Apis mellifera, are important pollinators of the highbush blueberry variety Ventura despite the inability to sonicate
Authors: Martin Keanu , Anderson Bruce , Minnaar Corneile , de Jager Marinus 
Published: February 2019

AbstractAnimal-mediated pollination is an essential ecosystem service which over a third of the world’s agricultural crops depend on. Blueberry fruit production is highly dependent on pollinators and in their native range they are pollinated mostly by bumble bees (Bombus spp.). Demand for blueberries has increased in recent years due to their perceived health benefits. Consequently, blueberry cultivation has expanded well beyond their native range, including several regions where bumble bees are not present. In many areas, honey bees may be the only commercially available pollinators of blueberries because many countries ban the importation of bumble bees. This study aimed to determine the benefits of honey bee pollination on blueberry fruit quality and quantity for the variety Ventura by comparing yields of honey-bee-pollinated flowers to flowers where pollinators had been excluded. Honey bees significantly increased berry mass and diameter. Our results suggest that the presence of honey bee pollinators potentially increases revenue by approximately $864 501/ha in areas without bumble bees. We conclude that Ventura is reliably pollinated by honey bees, and that honey bee pollination may be a useful substitute for bumble bees in areas where bumble bees are absent. We also determined the extent to which blueberry yields could still be improved by comparing fruit quality and quantity under honey bee pollination to fruit quality and quantity achieved through ideal hand pollination. We found that blueberry yields may be still be significantly increased relative to ideal hand pollination and we discuss potential ways to improve the efficiency of honeybee pollination in the future. Additional research is required to study how beneficial honey bees are to fruit yield on varieties as the benefits of honey bees are likely to vary across different varieties.
Environmental pheromone and endocrine signals correct heterochronic developmental phenotypes caused by insufficient expression oflet-7family microRNAs inC. elegans
Authors: Ilbay Orkan , Ambros Victor 
Published: February 2019

SummaryAdverse environmental conditions can affect rates of animal developmental progression and lead to temporary developmental quiescence (diapause), exemplified by the dauer larva stage of the nematodeCaenorhabditis elegans. Remarkably, patterns of cell division and temporal cell fate progression inC. eleganslarvae are not affected by changes in developmental trajectory. However, the underlying physiological and gene regulatory mechanisms that ensure robust developmental patterning despite substantial plasticity in developmental progression are largely unknown. Here, we report that diapause-inducing environmental pheromone and endocrine signals correct heterochronic developmental cell lineage defects caused by insufficient expression oflet-7family microRNAs inC. elegans.Two conserved endocrine signaling pathways, DAF-7/TGF-β and DAF-2/Insulin, that confer on the larva diapause/non-diapause alternative developmental trajectories, interact with the nuclear hormone receptor, DAF-12, to initiate and regulate a rewiring of the genetic circuitry controlling temporal cell fates. This rewiring includes: 1) repression of the DAF-12 ligand-activated expression oflet-7family microRNAs, and 2) engagement of a novel ligand-independent DAF-12 activity to downregulate the criticallet-7family target Hunchback-like-1 (HBL-1). This alternative HBL-1 downregulation program is responsible for correctinglet-7family insufficiency phenotypes and it requires the activities of certain heterochronic genes,lin-46, lin-4andnhl-2,that are previously associated with an altered genetic program in post-diapause animals. Our results show how environmental pheromones and endocrine signaling pathways can coordinately regulate both developmental progression and cell fate transitions inC. eleganslarvae under stress, so that the developmental schedule of cell fates remains unaffected by changes in developmental trajectory.
Functional ultrasound imaging of deep visual cortex in awake non-human primates
Authors: Kévin Blaize , Marc Gesnik , Fabrice Arcizet , Harry Ahnine , Ulisse Ferrari , Thomas Deffieux , Pierre Pouget , Frédéric Chavane , Mathias Fink , José-Alain Sahel , Mickael Tanter , Serge Picaud 
Published: February 2019

SummaryDeep regions of the brain are not easily accessible to investigation at the mesoscale level in awake animals or humans. We have recently developed functional Ultrasound (fUS) imaging fUS imaging technique to uncover deep hemodynamic functional responses. Applying fUS imaging on two awake non-human primates performing a passive fixation task, we reconstructed their retinotopic maps down to the deep calcarine and lunate sulci on visual areas (V1, V2 and V3). These maps were acquired in a single hour session with very few stimuli presentation. The spatial resolution of the technology is illustrated by mapping of Ocular Dominance (OD) columns within superficial and deep layers of the primary visual cortex. These acquisitions showed that OD selectivity is mostly present in layer IV but with evidence also in layers II/III and V. The fUS imaging technology therefore provides a new mesoscale approach to map brain activities at high spatiotemporal resolution in awake subjects within the whole depth of the cortex.
Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling
Authors: Gunner Georgia , Cheadle Lucas , Johnson Kasey M. , Ayata Pinar , Badimon Ana , Mondo Erica , Nagy Aurel , Liu Liwang , Bemiller Shane M. , Kim Ki-Wook , Lira Sergio A. , Lamb Bruce T. , Tapper Andrew R. , Ransohoff Richard M. , Greenberg Michael E. , Schaefer Anne , Schafer Dorothy P. 
Published: February 2019

AbstractMicroglia rapidly respond to changes in neural activity and inflammation to regulate synaptic connectivity. The extracellular signals, particularly neuron-derived molecules, that drive these microglial functions at synapses remains a key open question. Here, whisker lesioning, known to dampen cortical activity, induces microglia-mediated synapse elimination. We show that this synapse elimination is dependent on the microglial fractalkine receptor, CX3CR1, but not complement receptor 3, signaling. Further, mice deficient in the CX3CR1 ligand (CX3CL1) also have profound defects in synapse elimination. Single-cell RNAseq then revealed thatCx3cl1is cortical neuron-derived and ADAM10, a metalloprotease that cleaves CX3CL1 into a secreted form, is upregulated specifically in layer IV neurons and microglia following whisker lesioning. Finally, inhibition of ADAM10 phenocopiesCx3cr1-/-andCx3cl1-/-synapse elimination defects. Together, these results identify novel neuron-to-microglia signaling necessary for cortical synaptic remodeling and reveal context-dependent immune mechanisms are utilized to remodel synapses in the mammalian brain.
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

AbstractRestriction-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.
A Quasi Birth-and-Death Model For Tumor Recurrence
Authors: Santana Leonardo M. , Ganesan Shridar , Bhanot Gyan 
Published: February 2019

AbstractA 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.