bluuebunny/crossref_metadata_2025_split huggingface dataset:
Auditory cortex activity measured with functional near-infrared spectroscopy is susceptible to masking by cortical blood stealing
Authors: Steinmetzger Kurt , Shen Zhengzheng , Riedel Helmut , Rupp André 
Published: June 2020

ABSTRACTTo validate the use of functional near-infrared spectroscopy (fNIRS) in auditory perception experiments, combined fNIRS and electroencephalography (EEG) data were obtained from normal-hearing subjects passively listening to speech-like stimuli without linguistic content. The fNIRS oxy-haemoglobin (HbO) results were found to be inconsistent with the deoxy-haemoglobin (HbR) and EEG data, as they were dominated by pronounced cerebral blood stealing in anterior- to-posterior direction. This large-scale bilateral gradient in the HbO data masked the right-lateralised neural activity in the auditory cortex that was clearly evident in the HbR data and EEG source reconstructions. When the subjects were subsequently split into subgroups with more positive or more negative HbO responses in the right auditory cortex, the former group surprisingly showed smaller event-related potentials, less activity in frontal cortex, and increased EEG alpha power, all indicating reduced attention and vigilance. These findings thus suggest that positive HbO responses in the auditory cortex may not necessarily be a favourable result when investigating auditory perception using fNIRS. More generally, the results show that the interpretation of fNIRS HbO signals can be misleading and demonstrate the benefits of combined fNIRS-EEG analyses in resolving this issue.
A monogenic and fast-responding Light-Inducible Cre recombinase as a novel optogenetic switch
Authors: Duplus-Bottin Hélène , Spichty Martin , Triqueneaux Gérard , Place Christophe , Mangeot Philippe Emmanuel , Ohlmann Théophile , Vittoz Franck , Yvert Gaël 
Published: June 2020

ABSTRACTOptogenetics enables genome manipulations with high spatiotemporal resolution, opening exciting possibilities for fundamental and applied biological research. Here, we report the development of LiCre, a novel light-inducible Cre recombinase. LiCre is made of a single flavin-containing protein comprising the asLOV2 photoreceptor domain ofAvena sativafused to a Cre variant carrying destabilizing mutations in its N-terminal and C-terminal domains. LiCre can be activated within minutes of illumination with blue light, without the need of additional chemicals. When compared to existing photoactivatable Cre recombinases based on two split units, LiCre displayed faster and stronger activation by light as well as a lower residual activity in the dark. LiCre was efficient both in yeast, where it allowed us to control the production ofβ-carotene with light, and in human cells. Given its simplicity and performances, LiCre is particularly suited for fundamental and biomedical research, as well as for controlling industrial bioprocesses.
Use of signals of positive and negative selection to distinguish cancer genes and passenger genes
Authors: Bányai László , Trexler Mária , Kerekes Krisztina , Csuka Orsolya , Patthy László 
Published: June 2020

AbstractA major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most approaches focused on genes that are positively selected for mutations that drive carcinogenesis and neglected the role of negative selection. Some studies have actually concluded that negative selection has no role in cancer evolution. In the present work we have re-examined the role of negative selection in tumor evolution through the analysis of the patterns of somatic mutations affecting the coding sequences of human genes. Our analyses have confirmed that tumor suppressor genes are positively selected for inactivating mutations. Oncogenes, however, were found to display signals of both negative selection for inactivating mutations and positive selection for activating mutations. Significantly, we have identified numerous human genes that show signs of strong negative selection during tumor evolution, suggesting that their functional integrity is essential for the growth and survival of tumor cells.
Constitutional activation of BMP4 and WNT signalling in hESC results in impaired mesendoderm differentiation
Authors: Markouli C. , Couvreu De Deckersberg E. , Dziedzicka D. , Regin M. , Franck S. , Keller A. , Gheldof A. , Geens M. , Sermon K. , Spits C. 
Published: June 2020

AbstractWe identified a human embryonic stem cell subline that fails to respond to the differentiation cues needed to obtain mesendoderm derivatives, differentiating into trophoblast-like cells instead. RNA-sequencing analysis showed that the subline has hyperactivation of the WNT and BMP4 signalling. Modulation of these pathways with small molecules confirmed them as the cause of the differentiation impairment. While activation of WNT and BMP4 in control cells resulted in a loss of mesendoderm differentiation and induction of trophoblast markers, inhibition of these pathways in the subline restored its ability to differentiate. Karyotyping and exome sequencing analysis did not identify any changes in the genome that could account for the pathway deregulation. These findings add to the increasing evidence that different responses of stem cell lines to differentiation protocols are based on genetic and epigenetic factors, inherent to the line or acquired during cell culture.
Hierarchical disruption in the cortex of anesthetized monkeys as a new signature of consciousness loss
Authors: Signorelli Camilo Miguel , Uhrig Lynn , Kringelbach Morten , Jarraya Bechir , Deco Gustavo 
Published: June 2020

AbstractAnesthesia induces a reconfiguration of the repertoire of functional brain states leading to a high function-structure similarity. However, it is unclear how these functional changes lead to loss of consciousness. Here we suggest that the mechanism of conscious access is related to a general dynamical rearrangement of the intrinsic hierarchical organization of the cortex. To measure cortical hierarchy, we applied the Intrinsic Ignition analysis to resting-state fMRI data acquired in awake and anesthetized macaques. Our results reveal the existence of spatial and temporal hierarchical differences of neural activity within the macaque cortex, with a strong modulation by the depth of anesthesia and the employed anesthetic agent. Higher values of Intrinsic Ignition correspond to rich and flexible brain dynamics whereas lower values correspond to poor and rigid, structurally driven brain dynamics. Moreover, spatial and temporal hierarchical dimensions are disrupted in a different manner, involving different hierarchical brain networks. All together suggest that disruption of brain hierarchy is a new signature of consciousness loss.
Quantitative longitudinal predictions of Alzheimer’s disease by multi-modal predictive learning
Authors: Prakash M. , Abdelaziz M. , Zhang L. , Strange B.A. , Tohka J. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: June 2020

AbstractBackgroundQuantitatively predicting the progression of Alzheimer’s disease (AD) in an individual on a continuous scale, such as AD assessment scale-cognitive (ADAS-cog) scores, is informative for a personalized approach as opposed to qualitatively classifying the individual into a broad disease category. We hypothesize that multi-modal data and predictive learning models can be employed for longitudinally predicting ADAS-cog scores.MethodsMultivariate regression techniques were employed to model baseline multi-modal data (demographics, neuroimaging, and cerebrospinal fluid based markers, and genetic factors) and future ADAS-cog scores. Prediction models were subjected to repeated cross-validation and the resulting mean absolute error and cross-validated correlation of the model assessed.ResultsPrediction models on multi-modal data outperformed single modal data up to 36 months. Incorporating baseline ADAS-cog scores to prediction models marginally improved predictive performance.ConclusionsFuture ADAS-cog scores were successfully estimated via predictive learning aiding clinicians in identifying those at greater risk of decline and apply interventions at an earlier disease stage and inform likely future disease progression in individuals enrolled in AD clinical trials.
Secretion, maturation and activity of a quorum-sensing peptide (GSP) inducing bacteriocins transcription inStreptococcus gallolyticus
Authors: Harrington Anthony , Proutiere Alexis , Dramsi Shaynoor , Tal-Gan Yftah 
Published: June 2020

AbstractStreptococcus gallolyticussubsp.gallolyticus(Sgg) is an emerging opportunistic pathogen responsible for septicemia and endocarditis in the elderly. Invasive infections bySggare strongly linked to the occurrence of colorectal cancer (CRC). It was previously shown that increased secondary bile salts in CRC-conditions enhances the bactericidal activity of gallocin, a bacteriocin produced bySgg, enabling it to colonize the mouse colon by outcompeting resident enterococci. In a separate study, we have shown thatSggproduces and secretes a 21-mer peptide that activates bacteriocin production. This peptide was named CSP because of its sequence similarity with competence stimulating peptides found in other streptococci. Here we demonstrate that CSP is abona fidequorum-sensing peptide involved in activation of gallocin gene transcription. We therefore refer to CSP as GSP (gallocin stimulating peptide). GSP displays some unique features since itsN-terminal amino-acid lies three residues after the double glycine leader sequence. Herein, we set out to investigate the processing and export pathway that leads to mature GSP. We also conducted the first comprehensive structure-activity relationship (SAR) ofSggGSP to identify its key structural features.SignificanceStreptococcus gallolyticussubsp.gallolyticus(Sgg) is an opportunistic pathogen associated with colorectal cancer (CRC) and endocarditis.Sggutilizes quorum-sensing (QS) to regulate the production of a bacteriocin (gallocin) and gain selective advantage in colonizing the colon. In this manuscript, we report 1) the first structure-activty relationship study of theSggQS pheromone that regulates gallocin production; 2) evidence that the active QS pheromone is processed to its mature form by a unique ABC transporter and not processed by an extracellular protease; and 3) supporting evidence of interspecies interactions between streptococci pheromones. Our results revealed the minimal pheromone scaffold needed for gallocin activation and uncovered unique interactions between two streptococci species QS signals that warrant further studies.
Structure and assembly of CAV1 8S complexes revealed by single particle electron microscopy
Authors: Han Bing , Porta Jason C. , Hanks Jessica L. , Peskova Yelena , Binshtein Elad , Dryden Kelly , Claxton Derek P. , Mchaourab Hassane S. , Karakas Erkan , Ohi Melanie D. , Kenworthy Anne K. 
Published: June 2020

AbstractHighly stable oligomeric complexes of the monotopic membrane protein caveolin serve as fundamental building blocks of caveolae. Current evidence suggests these complexes are disc shaped, but the details of their structural organization and how they assemble are poorly understood. Here, we address these questions using single particle electron microscopy of negatively stained recombinant 8S complexes of human Caveolin-1. We show that 8S complexes are toroidal structures ~15 nm in diameter that consist of an outer ring, an inner ring, and central protruding stalk. Moreover, we map the position of the N- and C-termini and determine their role in complex assembly, and visualize the 8S complexes in heterologous caveolae. Our findings provide critical insights into the structural features of 8S complexes and allow us to propose a new model for how these highly stable membrane-embedded complexes are generated.
Crystal structure of a novel guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi
Authors: Lim Christopher , Berk Jason M. , Blaise Alyssa , Bircher Josie , Koleske Anthony J. , Hochstrasser Mark , Xiong Yong 
Published: June 2020

AbstractRho family GTPases regulate an array of cellular processes and are often modulated by pathogens to promote infection. Here, we identify a cryptic guanine nucleotide exchange factor (GEF) domain in the OtDUB protein encoded by the pathogenic bacterium Orientia tsutsugamushi. A proteomics-based OtDUB interaction screen identified numerous potential host interactors, including the Rho-GTPases Rac1 and Cdc42. We discovered a new domain in OtDUB with Rac1/Cdc42 GEF activity (OtDUBGEF), with higher activity toward Rac1 in vitro. While this GEF bears no obvious sequence similarity to known GEFs, crystal structures of OtDUBGEF alone (3.0 Å) and complexed with Rac1 (1.7 Å) reveal striking convergent evolution, with a distinct topology, on a V-shaped bacterial GEF fold shared with other bacterial GEF domains. Structure-guided mutational analyses identified residues critical for activity and a novel mechanism for nucleotide displacement. Ectopic expression of OtDUB activates Rac1 preferentially in cells, and expression of the OtDUBGEF alone alters cell morphology. Cumulatively, this work reveals a novel bacterial GEF within the multifunctional OtDUB that co-opts host Rac1 signaling to evoke changes in cytoskeletal structure.
Comparative MD simulations and advanced analytics based studies on wild-type and hot-spot mutant A59G HRas
Authors: Sharma Neeru , Sonavane Uddhavesh , Joshi Rajendra 
Published: June 2020

AbstractThe Ras family of proteins is known to play an important role in cellular signal transduction. The oncoprotein Ras is also found to be mutated in ∼90% of the pancreatic cancers, of which G12V, G13V, A59G and Q61L are the known hot-spot mutants. These ubiquitous proteins fall in the family of G-proteins, and hence switches between active GTP bound and inactive GDP bound states, which is hindered in most of its oncogenic mutant counterparts. Moreover, Ras being a GTPase has an intrinsic property to hydrolyze GTP to GDP, which is obstructed due to mutations and lends the mutants stuck in constitutively active state leading to oncogenic behavior. In this regard, the present study aims to understand the dynamics involved in the hot-spot mutant A59G-Ras using long classical MD simulations (∼10µs) and comparing the same with its wild-type counterpart. Advanced analytics using Markov State Model (MSM) based approach has been deployed to comparatively understand the transition path for the wild-type and mutant systems. Roles of crucial residues like Tyr32, Gln61 and Tyr64 have also been established using multivariate PCA analyses. Furthermore, this multivariate PCA analysis also provides crucial features which may be used as reaction coordinates for biased simulations for further studies. The absence of formation of pre-hydrolysis network is also reported for the mutant conformation, using the distance-based analyses (between crucial residues) of the conserved regions. The implications of this study strengthen the hypothesis that the disruption of the pre-hydrolysis network in the mutant A59G ensemble might lead to permanently active oncogenic conformation in the mutant conformers.
A tale of two fish: Comparative transcriptomics of resistant and susceptible steelhead following exposure toCeratonova shastahighlights differences in parasite recognition
Authors: Barrett Damien , Bartholomew Jerri L. 
Published: June 2020

AbstractDiseases caused by myxozoan parasites represent a significant threat to the health of salmonids in both the wild and aquaculture setting, and there are no effective therapeutants for their control. The myxozoanCeratonova shastais an intestinal parasite of salmonids that causes severe enteronecrosis and mortality. Most fish populations appear genetically fixed as resistant or susceptible to the parasite, offering an attractive model system for studying the immune response to myxozoans. We hypothesized that early recognition of the parasite is a critical factor driving resistance and that susceptible fish would have a delayed immune response. RNA-seq was used to identify genes that were differentially expressed in the gills and intestine during the early stages ofC. shastainfection in both resistant and susceptible steelhead(Oncorhynchus mykiss).This revealed a downregulation of genes involved in the IFN-γ signaling pathway in the gills of both phenotypes. Despite this, resistant fish quickly contained the infection and several immune genes, including two innate immune receptors were upregulated. Susceptible fish, on the other hand, failed to control parasite proliferation and had no discernible immune response to the parasite, including a near-complete lack of differential gene expression in the intestine. Further sequencing of intestinal samples from susceptible fish during the middle and late stages of infection showed a vigorous yet ineffective immune response driven by IFN-γ, and massive differential expression of genes involved in cell adhesion and the extracellular matrix, which coincided with the breakdown of the intestinal structure. Our results suggest that the parasite may be suppressing the host’s immune system during the initial invasion, and that susceptible fish are unable to recognize the parasite invading the intestine or mount an effective immune response. These findings improve our understanding of myxozoan-host interactions while providing a set of putative resistance markers for future studies.
Combination of favorable gene haplotypes plays an important role in rice hybrid grain quality traits based on genome-wide association analysis
Authors: Li Lanzhi , Zheng Xingfei , Zhang Xueli , Xu Kai , Song Shufeng , Su Jing , Wu Chao , Li Zirong , Tang Wenbang , Diao Ying , Tang Zhonghai , Yuan Zheming , Hu Zhongli 
Published: June 2020

SummaryYield level and grain quality determine the commercial potential of rice (Oryza sativaL.) varieties. Mining and using genes that control important rice grain quality characteristics are major tasks for plant breeders. Here, a genome-wide association study was conducted to determine the genetic bases of 12 rice grain quality traits in 113 varieties and 565 testcross hybrids. A total of 56 significant SNPs were associated with 9 of the traits in variety phenotypic, general combining ability, testcross hybrid phenotypic and mid-parental heterotic datasets, from which 45 novel loci were identified. The cumulative effects of superior alleles or favorable haplotypes of genes closest to significant quality trait-associated loci were found in the four datasets. Additionally, the favorable gene haplotypes performed better than those of superior alleles in the variety and testcross hybrid datasets. Pyramiding the favorable haplotypes of five cloned rice grain quality genes resulted in a very low amylose content and high yield in the latter. These testcross hybrids had rice grain qualities similar to their parental lines but with much higher yields. The amylose content, grain width and grain length predictions for potential hybrids among the 113 varieties using genomic selection based on the BayesB method revealed a performance trend similar to those the testcross hybrids in our study. Thus, the selection of combination of favorable rice quality-related gene haplotypes is recommended to breed hybrids with high yields and elite grain qualities.
2D or Not 2D? An FMRI Study of How Dogs Visually Process Objects
Authors: Prichard Ashley , Chhibber Raveena , Athanassiades Kate , Chiu Veronica , Spivak Mark , Berns Gregory S. 
Published: June 2020

ABSTRACTGiven humans’ habitual use of screens, they rarely consider potential differences when viewing two dimensional (2D) stimuli and real-world versions of dimensional stimuli. Dogs also have access to many forms of screens and touch pads, with owners even subscribing to dog-directed content. Humans understand that 2D stimuli are representations of real-world objects, but do dogs? In canine cognition studies, 2D stimuli are almost always used to study what is normally 3D, like faces, and may assume that both 2D and 3D stimuli are represented in the brain the same way. Here, we used awake fMRI of 15 dogs to examine the neural mechanisms underlying dogs’ perception of two- and three-dimensional objects after the dogs were trained on either a two- or three-dimensional version of the objects. Activation within reward processing regions and parietal cortex of the dog brain to 2D and 3D versions of objects was determined by their training experience, as dogs trained on one dimensionality showed greater activation to the dimension on which they were trained. These results show that dogs do not automatically generalize between two- and three-dimensional stimuli and caution against implicit assumptions when using pictures or videos with dogs.
Is Overfishing the Main or Only Factor in Fishery Resource Decline? The Case of The Magdalena River Fishery and Its Correlation with Anthropic Pressures
Authors: Hernández-Barrero Sandra , Barco Mauricio Valderrama , Barreto Reyes Carlos Guillermo , Sierra Luis Sierra , Stotz Wolfgang 
Published: June 2020

AbstractOverfishing has been historically considered as the main cause of fish stock depletion worldwide. This paradigm has oriented fishery management towards a classical approach, under which externalities to fisheries were not considered as they were difficult to assess and measure. The aim of this study is to describe the dynamics of different environmental, economic, and demographic variables (water flow, forest cover, gold production, population growth, stored water volume, and sediments) in relation to the behavior of the fishery production in the Magdalena-Cauca river basin from 1980 to 2015. Generalized Additive Models were used to determine the variables that best explain fishery production. The findings confirmed that environmental deterioration of the Magdalena River basin explained at least 60% of the reduction in fishery production. Thus, we concluded that the traditional approach of making fishers responsible for the decline of fish production was a misguided argument, and before implementing restrictions on fishing activity, a better understanding of the overall system is crucial. Hence, fishery management should involve the economic and social sectors that affect the offer of ecosystem services within the basin, including fishing.
Biosynthesis of silver nanoparticles and exopolysaccharide using novel Thermophilic strain (Ts-1) ofBacillus amyloliquefaciens
Authors: Thota Sharath Chandra , Sreelatha Bathini 
Published: June 2020

AbstractIn the developing world, Nanotechnology became an efficient method in therapeutics, antimicrobials, diagnostics, catalysis, microelectronics, and high sensitivity biomolecular detection. As well as on the other hand, Exopolysaccharides are biopolymers which are also widely used in food formulation, bio- flocculants, bio-absorbents, drug delivery agents. As the chemical methods of synthesizing nanoparticles and polymers are environmentally risky, costly, and toxic. In the present study, we focused on production, purification, and characterization of silver nanoparticles (AgNPs) and exopolysaccharide (EPS) by eco-friendly, extracellular biosynthetic methods using novel thermophilicBacillus amyloliquefaciensstrain Ts-1. This strain was isolated from soil samples by employing pour and spread plate techniques. After obtaining pure culture, the bacterium was used for the synthesis of AgNPs and EPS. Nanoparticles were synthesized from AgNO3by using reducing agents secreted by bacteria, and Exopolysaccharide biosynthesis is carried out in three steps by the organism in the presence of a carbon source. Synthesis of colloidal AgNPs and EPS was monitored by UV-Visible spectroscopy and Visual observation, respectively. SEM, Edax and FTIR were performed for the characterization of the AgNPs and EPS such as their size, morphology and composition and we also showed the catalytic activity of AgNps in degradation of methylene blue.