bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fungal-bacterial interaction selects for quorum sensing mutants and a metabolic shift towards the production of natural antifungal compounds
Authors: Albarracín Orio Andrea G. , Petras Daniel , Tobares Romina A. , Aksenov Alexander A. , Wang Mingxun , Juncosa Florencia , Sayago Pamela , Moyano Alejandro J. , Dorrestein Pieter C. , Smania Andrea M. , Ducasse Daniel A. 
Published: July 2018

AbstractEnvironmental species of bacteria and fungi coexist and interact showing antagonistic and mutualistic behaviors, mediated by exchange of small diffusible metabolites, driving microbial adaptation to complex communal lifestyles1. Here we show that a wild Bacilus subtilis strain undergoes heritable phenotypic variation following interaction with the soil fungal pathogen Setophoma terrestris (ST) in co-culture. Metabolomics analysis revealed a differential profile in B. subtilis before (pre-ST) and after (post-ST) interacting with the fungus, which paradoxically involved the absence of lipopeptides surfactin and plipastatin and yet acquired antifungal activity in post-ST variants. Metabolic changes were also observed in the profile of volatile compounds, with 2-heptanone and 2-octanone being the most discriminating metabolites present at higher concentrations in post-ST during its interaction with the fungus. Most strikingly, both ketones showed strong antifungal activity against S. terrestris, which was lost with the addition of exogenous surfactin to the medium. Whole-genome analyses showed that mutations in the comA and comP genes of the ComQPXA quorum-sensing system, constituted the genetic bases of post-ST conversion, which allowed the concomitant production of ketones and elimination of surfactin. These findings suggest that mutations in ComQXPA stably rewired B. subtilis metabolism towards the depletion of surfactins and the production of antifungal compounds during its antagonistic interaction with S. terrestris.
SGC-GAK-1: a chemical probe for cyclin G associated kinase (GAK)
Authors: Asquith Christopher R. M. , Berger Benedict-Tilman , Wan Jing , Bennett James M. , East Michael P. , Elkins Jonathan M. , Fedorov Oleg , Godoi Paulo H. , Hunter Debra M. , Knapp Stefan , Müller Susanne , Wells Carrow I. , Earp H. Shelton , Willson Timothy M. , Zuercher William J. 
Published: July 2018

AbstractWe describe SGC-GAK-1 (11), a potent, selective, and cell-active inhibitor of cyclin G associated kinase (GAK), together with a structurally-related negative control SGC-GAK-1N (14). SGC-GAK-1 is highly selective in a kinome-wide screen, but cellular engagement assays defined RIPK2 as a collateral target. We identified 18 as a potent inhibitor of RIPK2 lacking GAK activity. Together, the chemical probe set of 11, 14, and 18 can be used to interrogate the cellular biology of GAK inhibition.
Cell-type specific patterned stimulus-independent neuronal activity in theDrosophilavisual system during synapse formation
Authors: Akin Orkun , Bajar Bryce T. , Keles Mehmet F. , Frye Mark A. , Zipursky S. Lawrence 
Published: July 2018

SummaryStereotyped synaptic connections define the neural circuits of the brain. In vertebrates, stimulus-independent activity contributes to neural circuit formation. It is unknown whether this type of activity is a general feature of nervous system development. Here, we report patterned, stimulus-independent neural activity in theDrosophilavisual system during synaptogenesis. Usingin vivocalcium, voltage, and glutamate imaging, we found that all neurons participate in this spontaneous activity, which is characterized by brain-wide periodic active and silent phases. Glia are active in a complementary pattern. Each of the 15 examined of the over 100 specific neuron types in the fly visual system exhibited a unique activity signature. The activity of neurons that are synaptic partners in the adult was highly correlated during development. We propose that this cell type-specific activity coordinates the development of the functional circuitry of the adult brain.
Does the heart forget? Modulation of cardiac activity induced by inhibitory control over emotional memories
Authors: Legrand Nicolas , Etard Olivier , Vandevelde Anaïs , Pierre Mélissa , Viader Fausto , Clochon Patrice , Doidy Franck , Peschanski Denis , Eustache Francis , Gagnepain Pierre 
Published: July 2018

AbstractEffort to suppress past experiences from conscious awareness can lead to forgetting. It remains largely unknown whether emotions, including their physiological causes, are also impacted by such memory suppression. In two studies, we measured in healthy participants the aftereffect of suppressing negative memories on cardiac response. Results of Study 1 revealed that an efficient control of memories was associated with a long-term inhibition of the cardiac deceleration normally induced by disgusting stimuli. Attempts to suppress sad memories, on the opposite, aggravated cardiac response, an effect that was largely related to the inability to forget this specific material. In Study 2, we found using electroencephalography that a prominent neural marker of inhibitory control, a suppression of the 5-9 Hz frequency band, was related to the subsequent inhibition of the cardiac response. These results demonstrate that suppressing memories also influence the cardiac system, opening new avenues for treating intrusive memories.
Complexity of Brain Activity and Connectivity in Functional Neuroimaging
Authors: Dimitriadis Stavros I. 
Published: July 2018

AbstractUnderstanding the complexity of human brain dynamics and brain connectivity across the repertoire of functional neuroimaging and various conditions, is of paramount importance. Novel measures should be designed tailored to the input focusing on multichannel activity and dynamic functional brain connectivity (DFBC).Here, we defined a novel complexity index (CI) from the field of symbolic dynamics that quantifies patterns of different words up to a length from a symbolic sequence. The CI characterizes the complexity of the brain activity.We analysed dynamic functional brain connectivity by adopting the sliding window approach using imaginary part of phase locking value (iPLV) for EEG/ECoG/MEG and wavelet coherence (WC) for fMRI. Both intra and cross-frequency couplings (CFC) namely phase-to-amplitude were estimated using iPLV/WC at every snapshot of the DFBC. Using proper surrogate analysis, we defined the dominant intrinsic coupling mode (DICM) per pair of regions-of-interest (ROI). The spatio-temporal probability distribution of DICM were reported to reveal the most prominent coupling modes per condition and modality. Finally, a novel flexibility index is defined that quantifies the transition of DICM per pair of ROIs between consecutive time-windows.The whole methodology was demonstrated using four neuroimaging datasets (EEG/ECoG/MEG/fMRI).Finally, we succeeded to totally discriminate healthy controls from schizophrenic using FI and dynamic reconfiguration of DICM. Anesthesia independently of the drug caused a global decreased of complexity in all frequency bands with the exception in δ and alters the dynamic reconfiguration of DICM. CI and DICM of MEG/fMRI resting-state recordings in two spatial scales were high reliable.Significant StatementIn the present study, we demonstrated novel indexes for the estimation of complexity in both raw brain activity and dynamic functional connectivity. To ort the universality of both indexes for the majority of functional neuroimaging modalities, we adopted open datasets from electro and magneto-encephalography, from electro-corticography and functional magnetic resonance imaging. Both indexes proved informative and reliable across repeat scan sessions. Moreover, we succeeded to totally discriminate with absolute accuracy healthy controls from schizophrenic patients. Both indexes proved sensitive to common anesthetic drugs effect in monkeys and reliable in MEG and fMRI repeat scan sessions. We first reported the notion of cross-frequency coupling in BOLD activity. Our analysis could be adapted it in any task and modality for any hypothesis driven study.
Muscle nonshivering thermogenesis in a feral mammal
Authors: Nowack Julia , Vetter Sebastian G. , Stalder Gabrielle , Painer Johanna , Kral Maria , Smith Steve , Le Minh Hien , Jurcevic Perica , Bieber Claudia , Arnold Walter , Ruf Thomas 
Published: July 2018

AbstractWhile small mammals and neonates are able to maintain an optimal body temperature (Tb) independent of ambient conditions by producing heat via nonshivering thermogenesis (NST) in the brown adipose tissue (BAT), larger mammals and other mammals lacking BAT were long believed to rely primarily on shivering and behavioural adaptations. However, recently, a second mechanism of NST was found in skeletal muscle that could play an important role in thermoregulation of such species. Muscle NST is independent of muscle contractions and produces heat based on the activity of an ATPase pump in the sarcoplasmic reticulum (SERCA1a) and controlled by the protein sarcolipin. To evaluate whether muscle NST could indeed play an important role in thermoregulation in species lacking BAT, we investigated the thermogenic capacities of new-born wild boar piglets. During cold exposure over the first 5 days of life, total heat production was improved while shivering intensity decreased, indicating an increasing contribution of NST. Sampling skeletal muscle tissue for analyses of SERCA activity as well as gene expression of SERCA1a and sarcolipin, we found an age-related increase in all three variables as well as in Tb. Hence, the improved thermogenesis during the development of wild boars is not due to shivering but explained by the observed increase in SERCA activity. Our results suggest that muscle NST may be the primary mechanism of heat production during cold stress in large mammals lacking BAT, strengthening the hypothesis that muscle NST has likely played an important role in the evolution of endothermy.
The effects and mechanism of peiminine-induced apoptosis in human hepatocellular carcinoma HepG2 cells
Authors: Chao Xu , Wang Guoquan , Tang Yuping , Dong Changhu , Li Hong , Wang Bin , Wu Jieqiong , Zhao Jiarong 
Published: July 2018

AbstractPeiminine is a compound that is isolated fromBolbostemma paniculatum(Maxim) Franquet (Cucurbitaceae family), which has demonstrated antitumor activities. Its precise molecular mechanisms underlying antitumor activity remain elusive. In this study, peiminine-induced apoptosis towards human hepatocellular carcinoma and its molecular mechanisms were investigated. MTT assay was employed to assess anticancer effects of peiminine at concentrations of 2, 4, 6, 8, 10, 12, and 14 μg/ml after 24, 48, or 72 h. Nuclear staining and flow cytometry were carried out to further assess apoptosis. Mitochondrial membrane potential evaluation and Western blot analysis were performed to investigate the mechanism of peiminine-induced apoptosis. Peiminine reduced the viability of HepG2 cells in a time- and dose-dependent manner and had an IC50of 4.58 μg/mL at 24h. Flow cytometry assessment indicated that peiminine markedly increased the cell number of apoptotic cells and the mitochondrial membrane potential dose-dependently in HepG2 cells. The results of Western blotting showed the expression of Bcl-2, procaspase-3, procaspase-8, procaspase-9, and PARP1decreased in HepG2 cells treated with peiminine, while the expression of Bax, caspase-3, caspase-8, caspase-9, and cleaved PARP1increased. The result suggest taht peiminine can induce apoptosis in human hepatocellular carcinoma HepG2 cells through both extrinsic and intrinsic apoptotic pathways.
Multiple roles of the non-structural protein 3 (nsP3) alphavirus unique domain (AUD) during Chikungunya virus genome replication and transcription
Authors: Gao Yanni , Goonawardane Niluka , Tuplin Andrew , Harris Mark 
Published: July 2018

AbstractChikungunya virus (CHIKV) is a re-emergingAlphaviruscausing fever, joint pain, skin rash, arthralgia, and occasionally death. Antiviral therapies and/or effective vaccines are urgently required. CHIKV biology is poorly understood, in particular the functions of the non-structural protein 3 (nsP3). Here we present the results of a mutagenic analysis of the alphavirus unique domain (AUD) of nsP3. Informed by the structure of the Sindbis virus AUD and an alignment of amino acid sequences of multiple alphaviruses, a series of mutations in the AUD were generated in a CHIKV sub-genomic replicon. This analysis revealed an essential role for the AUD in CHIKV RNA replication, with mutants exhibiting species- and cell-type specific phenotypes. To test if the AUD played a role in other stages of the virus lifecycle, the mutant panel was also analysed in the context of infectious CHIKV. Results indicated that, in addition to a role in RNA replication, the AUD was also required for virus assembly. Further analysis revealed that one mutant (P247A/V248A) specifically blocked transcription of the subgenomic RNA leading to a dramatic reduction in synthesis of the structural proteins and concomitant reduction in virus production. This phenotype could be explained by both a reduction in the binding of the P247A/V248A mutant nsP3 to viral genomic RNAin vivo, and the reduced affinity of the mutant AUD for the subgenomic promoter RNAin vitro.We propose that the AUD is a pleiotropic protein domain, with multiple functions during CHIKV RNA synthesis.Author summaryChikungunya virus (CHIKV) is an emerging threat to world health. It is transmitted by Aedes species mosquitos, and has caused massive epidemics across the globe. The virus causes fever, rash, arthritis and can sometimes be fatal. The biology of CHIKV is poorly understood, to address this deficiency we aimed to identify functions of one of the viral proteins, nsP3. We focussed on the central part of this protein, termed the alphavirus unique domain (AUD) because it is unique to the genus of viruses to which CHIKV belongs – theAlphaviruses– and not present in other related viruses. By making changes (mutations) in the AUD and analysing the effects of these changes we show that it is involved in multiple stages of the virus lifecycle. These observations identify nsP3 and the AUD in particular as a potential target for antiviral therapy or rational vaccine design.
Evaluation of InSeq to Identify Genes Essential for Pseudomonas aeruginosa PGPR2 Corn Root Colonization
Authors: Sivakumar Ramamoorthy , Ranjani Jothi , Vishnu Udayakumar S. , Jayashree Sathyanarayanan , Lozano Gabriel L. , Miles Jessica , Broderick Nichole A. , Guan Changhui , Gunasekaran Paramasamy , Handelsman Jo , Rajendhran Jeyaprakash 
Published: July 2018

AbstractThe reciprocal interaction between rhizosphere bacteria and their plant hosts results in a complex battery of genetic and physiological responses. In this study, we used insertion sequencing (INSeq) to reveal the genetic determinants responsible for the fitness of Pseudomonas aeruginosa PGPR2 during root colonization. We generated a random transposon mutant library of Pseudomonas aeruginosa PGPR2 comprising 39,500 unique insertions and identified genes required for growth in culture and on corn roots. A total of 108 genes were identified as contributing to the fitness of strain PGPR2 on roots. The importance in root colonization of four genes identified in the TnSeq screen was verified by constructing deletion mutants in the genes and testing them for the ability to colonize corn roots singly or in competition with the wild type. All four mutants were affected in corn root colonization, displaying 5-to 100-fold reductions in populations in single inoculations, and all were outcompeted by the wild type by almost 100-fold after seven days on corn roots in mixed inoculations of the wild type and mutant. The genes identified in the screen had homology to genes involved in amino acid catabolism, stress adaptation, detoxification, signal transduction, and transport. INSeq technology proved a successful tool to identify fitness factors in P. aeruginosa PGPR2 for root colonization.
Why is cancer not more common? A changing microenvironment may help to explain why, and suggests strategies for anti-cancer therapy
Authors: Jiang Xiaowei , Tomlinson Ian P.M. 
Published: July 2018

AbstractOne of the great unsolved puzzles in cancer biology is not why cancers occur, but rather, explaining why so few cancers occur compared with the theoretical number that could occur given the number of progenitor cells in the body and the normal mutation rate. We hypothesised that a contributory explanation is that the tumour microenvironment (TME) is not fixed, and that this could impair the ability of neoplastic cells to retain a high enough fitness to become a cancer. The TME has implicitly been assumed to be static in most cancer evolution models, and we therefore developed a mathematical model of spatial cancer evolution assuming that the TME, and thus the optimum cancer phenotype, change over time. Based on simulations, we show how cancer cell populations adapt to diverse changing TME conditions and fitness landscapes. Compared with static TMEs which generate neutral dynamics, changing TMEs lead to complex adaptations with spatio-temporal heterogeneity involving variable sub-clonal fitness, mixing, competition and phylogeny patterns. In many cases, cancer cell populations fail to grow or undergo spontaneous regression, and even extinction. Our analyses predict that cancer evolution in a changing TME is challenging, and can help to explain why cancer is neither inevitable nor as common as expected. Should cancer driver mutations with effects dependent of the TME exist, they are likely to be selected. Anti-cancer prevention and treatment strategies based on changing the TME are feasible and potentially effective.
Social stress as a priming mechanism for Thermal Tolerance During a Poleward Range Shift
Authors: Wood Connor , Fitt Robert N. L. , Lancaster Lesley T. 
Published: July 2018

AbstractCold tolerance plays a critical role in determining species’ geographical range limits. Previous studies have found that range shifts in response to climate warming are facilitated by cold acclimation capacities, due to increasingly colder and variable weather at high latitudes, and that cold tolerance can also be influenced by social factors. In this study we combined experiments and field studies to investigate the climatic and social factors affecting cold tolerances in range-shifting populations of the female-polymorphic damselflyIschnura elegansin northeast Scotland. In the field, we observed both environmental (measured via habitat suitability) and social (sex ratio and density) effects on cold tolerance (CTmin). Androchrome females (male-like females) were less susceptible to beneficial social effects on cold tolerance than gynochromes (female-like females), and correspondingly, gynochrome frequency increased at colder, environmentally-limiting sites towards the range margin. Our manipulations of density in the laboratory further provide novel, experimental evidence that social interactions directly impact cold tolerance n this species. These results suggest that reciprocal effects of social environments on thermal acclimation may be an important but commonly overlooked aspect of allee effects which contribute to the formation of range margins. Moreover, our results point to a wider need to consider the role of population and social dynamics to shape both the thermal physiology of individuals and the thermal niches of species.
Enforced expression of phosphatidylinositol 4-phosphate 5-kinase homolog (PIPKH) alters phosphatidylinositol 4,5-bisphosphate distribution and the localization of small G-proteins
Authors: Yang Yanbo , Park Miriam , Fairn Gregory D. 
Published: July 2018

AbstractThe generation of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) by phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) is essential for many of the functions including the control of cytoskeleton, signal transduction and endocytosis. Additionally, due to its presence in the plasma membrane and its anionic charge PtdIns(4,5)P2, together with phosphatidylserine, imbue the inner leaflet of the plasma membrane with a negative surface charge. This negative charge helps to define the identity of the plasma membrane as serves to recruit or regulate a multitude of proteins that contain polybasic domains or patches. Here we determine that the phosphatidylinositol 4-phosphate 5-kinase homolog (PIPKH) alters the subcellular distribution of PtdIns(4,5)P2 by re-localizing the PIP5Ks to endomembranes. Consistently, we find a redistribution of the PIP5K family members to endomembrane structures upon PIPKH overexpression that is accompanied by an accumulation of PtdIns(4,5)P2 and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), which further influences the distribution of endosomes and lysosomes. Additionally, we demonstrate that the accumulation of polyphosphoinositides increases their negative surface charge that in turn leads to the relocalization of surface charge probes as well as the polycationic proteins K-Ras and Rac1.
What determines bank interest rate spread? Evidence from Sub-Saharan Africa
Authors: Tarus Daniel Kipkirong , Manyala Philip Otieno 
Published: July 2018

PurposeThe purpose of this paper is to examine the determinants of bank interest rate spread in Sub-Saharan African countries, which were categorized into macro-specific, bank-specific and institutional variables.Design/methodology/approachThe authors used fixed effects estimations to analyze the data. The data were drawn from a pool of 20 Sub-Saharan African countries for a period of ten years spanning 2003–2012. The countries were categorized into low-income, lower middle-income and upper middle-income countries based on World Bank income classifications.FindingsThe results show that inflation has a negative and significant effect on interest rate spread, while operating costs and bank concentration have a positive and significant effect on interest rate spread. Similarly, government effectiveness, rule of law and political stability are negatively related to the interest rate spread.Practical implicationsThe paper provides evidence that interest rate spread is determined by both bank-specific, macro-economic and institutional variables. The paper also indicates that the income status of a country is important in explaining the variations in the interest rate spread across the region. Therefore, the policy makers should design policies that take into account the variables in order to help in planning by all economic agents, including banks.Originality/valueThe paper uses data from Sub-Saharan Africa and introduces institutional variables in the model, which have been found to be critical in the context.