bluuebunny/crossref_metadata_2025 huggingface dataset:
Using imaging photoplethysmography for heart rate estimation in non-human primates
Authors: Unakafov Anton M. , Möller Sebastian , Kagan Igor , Gail Alexander , Treue Stefan , Wolf Fred
Published: January 2018

For humans and for non-human primates heart rate is a reliable indicator of an individual’s current physiological state, with applications ranging from health checks to experimental studies of cognitive and emotional state. In humans, changes in the optical properties of the skin tissue correlated with cardiac cycles (imaging photoplethysmogram, iPPG) allow non-contact estimation of heart rate by its proxy, pulse rate. Yet, there is no established simple and non-invasive technique for pulse rate measurements in awake and behaving animals. Using iPPG, we here demonstrate that pulse rate in rhesus monkeys can be accurately estimated from facial videos. We computed iPPGs from seven color facial videos of three awake head-stabilized rhesus monkeys. Pulse rate estimated from iPPGs was in good agreement with reference data from a pulse-oximeter with error of pulse rate estimation below 5% for 82% of all epochs, and below 10% for 98% of the epochs. We conclude that iPPG allows non-invasive and non-contact estimation of pulse rate in non-human primates, which is useful for physiological studies and can be used toward welfare-assessment of non-human primates in research.
UniLoc: A universal protein localization site predictor for eukaryotes and prokaryotes
Authors: Lin Hsin-Nan , Chen Ching-Tai , Sung Ting-Yi , Hsu Wen-Lian
Published: January 2018

There is a growing gap between protein subcellular localization (PSL) data and protein sequence data, raising the need for computation methods to rapidly determine subcellular localizations for uncharacterized proteins. Currently, the most efficient computation method involves finding sequence-similar proteins (hereafter referred to assimilar proteins) in the annotated database and transferring their annotations to the target protein. When a sequence-similarity search fails to find similar proteins, many PSL predictors adopt machine learning methods for the prediction of localization sites. We proposed a universal protein localization site predictor - UniLoc - to take advantage of implicit similarity among proteins through sequence analysis alone. The notion of related protein words is introduced to explore the localization site assignment of uncharacterized proteins. UniLoc is found to identify useful template proteins and produce reliable predictions when similar proteins were not available.
Noradrenaline modulates decision urgency during sequential information gathering
Authors: Hauser Tobias U. , Moutoussis Michael , Purg Nina , Dayan Peter , Dolan Raymond J.
Published: January 2018

Arbitrating between timely choice and extended information gathering is critical in effective decision making. Aberrant information gathering behaviour is said to be a feature of psychiatric disorders such as schizophrenia and obsessive-compulsive disorder. We know little about the neurocognitive control mechanisms that drive such information gathering. In a double-blind placebo-controlled drug study with 60 healthy humans (30 female), we examined the effects of noradrenaline and dopamine antagonism on information gathering. We show that modulating noradrenaline function with propranolol leads to decreased information gathering behaviour and this contrasts with no effect following a modulation of dopamine function. Using a Bayesian computational model, we show sampling behaviour is best explained when including an urgency signal that promotes commitment to an early decision. We demonstrate that noradrenaline blockade promotes the expression of this decision-related urgency signal during information gathering. We discuss the findings with respect to psychopathological conditions that are linked to aberrant information gathering.

Significance Statement

Knowing when to stop gathering information and commit to an option is non-trivial. This is an important element in arbitrating between information gain and energy conservation. In this double-blind, placebo-controlled drug study, we investigated to role of catecholamines noradrenaline and dopamine on sequential information gathering. We found that blocking noradrenaline led to a decrease in information gathering, with no effect seen following dopamine blockade. Using a Bayesian computational model, we show that this noradrenaline effect is driven by an increased decision urgency, a signal that reflects an escalating subjective cost of sampling. The observation that noradrenaline modulates decision urgency suggests new avenues for treating patients that show information gathering deficits.
Vascular plants are strong predictors of multi-taxon species richness
Authors: Brunbjerg Ane Kirstine , Bruun Hans Henrik , Dalby Lars , Fløjgaard Camilla , Frøslev Tobias G. , Thomas Høye Toke , Goldberg Irina , Læssøe Thomas , Hansen Morten D. D. , Brøndum Lars , Skipper Lars , Fog Kåre , Ejrnæs Rasmus
Published: January 2018

Plants regulate soils and microclimate, provide substrate for heterotrophic taxa, are easy to observe and identify and have a stable taxonomy, which strongly justifies the use of plants as bioindicators in monitoring and conservation. However, insects and fungi make up the vast majority of species. Surprisingly, it remains untested whether plants are strong predictors of total multi-taxon species richness. To answer this question, we collected an extensive data set on species richness of vascular plants, bryophytes, macrofungi, lichens, plant-galling arthropods, gastropods, spiders, carabid beetles, hoverflies and OTU richness from environmental DNA metabarcoding. Plant species richness per se was a moderate predictor of richness of other taxa. Taking an ecospace approach to modelling, the addition of plant-derived bioindicators revealed 1) a consistently positive effect of plant richness on other taxa, 2) prediction of 12-55% of variation in other taxa and 48 % of variation in the total species richness.
A perceptual decision making EEG/fMRI data set
Authors: Georgie Yasmin K. , Porcaro Camillo , Mayhew Stephen D. , Bagshaw Andrew P. , Ostwald Dirk
Published: January 2018

We present a neuroimaging data set comprising behavioural, electroencephalographic (EEG), and functional magnetic resonance imaging (fMRI) data that were acquired from human subjects performing a perceptual decision making task. EEG data were acquired both independently and simultaneously with fMRI data. Potential data usages include the validation of biocomputational accounts of human perceptual decision making or the empirical validation of simultaneous EEG/fMRI data processing algorithms. The dataset is available from the Open Science Framework and organized according to the Brain Imaging Data Structure standard.
I judge you by your profit: Judgments of effort exerted by self and others are influenced by received rewards
Authors: Rollwage Max , Pannach Franziska , Stinson Caedyn , Toelch Ulf , Kagan Igor , Pooresmaeili Arezoo
Published: January 2018

Effort constitutes a major part of cost-benefit calculations underlying decision making. Therefore, estimating the effort someone has spent on a task is a core dimension for evaluating own and others’ actions. It has been previously shown that self-judgments of effort are influenced by the magnitude of obtained rewards. It is unclear, however, whether the influence of reward on effort estimations is limited to self-judgments or whether reward incorporation represents a general computational principle when judging effort. Here we show that people also integrate reward magnitude when judging the effort exerted by others. Participants (N=48) performed an effortful sensorimotor task interleaved with a partner, while rating either their own or the other person’s effort. After each trial but before the effort rating, both participants were informed about the obtained reward. We found that higher rewards led to higher estimations of exerted effort, in self-as well as other-judgments, and this effect was more pronounced for other-judgments. In both types of judgment, computational modelling revealed that reward information and the perceived level of exertion were combined in a Bayes optimal manner to form effort estimates. Remarkably, the extent to which rewards influenced effort judgments was positively correlated with conservative world-views, indicating that the basic computations underlying this behavioural phenomenon might be related to more general beliefs about the association between effort and reward in the society. The integration of reward information into retrospective effort judgments underscores the convergence of multiple information sources that supports adaptive learning and decision making in social contexts.
Metabarcoding analysis on European coastal samples reveals new molecular metazoan diversity
Authors: López-Escardó David , Paps Jordi , de Vargas Colomban , Massana Ramon , Ruiz-Trillo Iñaki , del Campo Javier
Published: January 2018

Although animals are among the best studied organisms, we still lack a full description of their diversity, especially for microscopic taxa. This is partly due to the time-consuming and costly nature of surveying animal diversity through morphological and molecular studies of individual taxa. A powerful alternative is the use of high-throughput environmental sequencing, providing molecular data from all organisms sampled. We here address the unknown diversity of animal phyla in marine environments using an extensive dataset designed to assess eukaryotic ribosomal diversity among European coastal locations. A multi-phylum assessment of marine animal diversity that includes water column and sediments, oxic and anoxic environments, and both DNA and RNA templates, revealed a high percentage of novel 18S rRNA sequences in most phyla, suggesting that marine environments have not yet been fully sampled at a molecular level. This novelty is especially high among Platyhelminthes, Acoelomorpha, and Nematoda, which are well studied from a morphological perspective and abundant in benthic environments. We also identified based on molecular data a potentially novel group of widespread tunicates. Moreover, we recovered a high number of reads for Ctenophora and Cnidaria in the smaller fractions suggesting their gametes might play a greater ecological role than previously suspected.
Inhibition of CaOx crystals byNeolamarckia cadamba: Anin vivoapproach
Authors: Prathibhakumari P.V , Prasad G.
Published: January 2018

The objective of the study was to find out the effectiveness of the methanol fruit extract ofN. cadambaon calcium oxalate induced nephrolithiasis in wistar albino rats. Animals were divided into nine groups (n=4) in which group 1 as control, group II as antilithiatic control and group III as lithiatic control. Dose for the methanol fruit extract was selected for the study as 200 and 400mg/kg body weight of fruit extract. Group IV and V were considered as post treatment groups and group VI to IX were co treatment groups. Ethylene glycol in drinking water was given to group II - IX for the induction of renal calculi. All the stone forming constituents such as urea, uric acid and creatinine were reduced significantly (p<0.01) in the extract treated groups. Calcium, oxalate and phosphorous concentrations in kidney were found to be diminished by the supplementation of extract. ICP-MS analysis, Histopathology, microcrystal study and pizzalato’s staining confirmed the efficacy of the fruit extract. In conclusion, the results suggested that the fruit extract is endowed with the property of an antilithiatic drug.
Neural engagement with online educational videos predicts learning performance for individual students
Authors: Cohen Samantha S. , Madsen Jens , Touchan Gad , Robles Denise , Lima Stella F. A. , Henin Simon , Parra Lucas C.
Published: January 2018

Online educational materials are largely disseminated through videos, and yet there is little understanding of how these videos engage students and fuel academic success. We hypothesized that components of the electroencephalogram (EEG), previously shown to reflect video engagement, would be predictive of academic performance in the context of educational videos. Two groups of subjects watched educational videos in either an intentional learning paradigm, in which they were aware of an upcoming test, or in an incidental learning paradigm, in which they were unaware that they would be tested. “Neural engagement” was quantified by the inter-subject correlation (ISC) of the EEG that was evoked by the videos. In both groups, students with higher neural engagement retained more information. Neural engagement also discriminated between attentive and inattentive video viewing. These results suggest that this EEG metric is a marker of the stimulus-related attentional mechanisms necessary to retain information. In the future, EEG may be used as a tool to design and assess online educational content.
Neuromagnetic signatures of the spatiotemporal transformation for manual pointing
Authors: Blohm G. , Alikhanian H. , Gaetz W. , Goltz H.C. , DeSouza J.F.X. , Cheyne D.O. , Crawford J.D.
Published: January 2018

Movement planning involves transforming the sensory goal representation into a command in motor coordinates. Surprisingly, the real-time dynamics of sensorimotor transformations at the whole brain level remain unknown, in part due to the spatiotemporal limitations of fMRI and neurophysiological recordings. Here, we used magnetoencephalography (MEG) during pro-/anti-wrist pointing to determine (1) the cortical areas involved in transforming visual signals into appropriate hand motor commands, and (2) how this transformation occurs in real time, both within and across the regions involved. We computed sensory, motor, and sensorimotor indices in 16 bilateral brain regions for direction coding based on hemispherically lateralized de/synchronization in the α (7-15Hz) and β (15-35Hz) bands. We found a visuomotor progression, from pure sensory codes in ‘early’ occipital-parietal areas, to a temporal transition from sensory to motor coding in the majority of parietal-frontal sensorimotor areas, to a pure motor code, in both the α and β bands. Further, the timing of these transformations revealed a top-down pro/anti cue influence that propagated ‘backwards’ from frontal through posterior cortical areas. These data directly demonstrate a progressive, real-time transformation both within and across the entire occipital-parietal-frontal network that follows specific rules of spatial distribution and temporal order.
qFit-ligand reveals widespread conformational heterogeneity of drug-like molecules in X-ray electron density maps
Authors: van Zundert Gydo C.P. , Hudson Brandi M. , Keedy Daniel A. , Fonseca Rasmus , Heliou Amelie , Suresh Pooja , Borrelli Kenneth , Day Tyler , Fraser James S. , van den Bedem Henry
Published: January 2018

Proteins and ligands sample a conformational ensemble that governs molecular recognition, activity, and dissociation. In structure-based drug design, access to this conformational ensemble is critical to understand the balance between entropy and enthalpy in lead optimization. However, ligand conformational heterogeneity is currently severely underreported in crystal structures in the Protein Data Bank, owing in part to a lack of automated and unbiased procedures to model an ensemble of protein-ligand states into X-ray data. Here, we designed a computational method, qFit-ligand, to automatically resolve conformationally averaged ligand heterogeneity in crystal structures, and applied it to a large set of protein receptor-ligand complexes. We found that up to 29 % of a dataset of protein crystal structures bound with drug-like molecules present evidence of unmodeled, averaged, relatively isoenergetic conformations in ligand-receptor interactions. In many retrospective cases, these alternate conformations were adventitiously exploited to guide compound design, resulting in improved potency or selectivity. Combining qFit-ligand with high-throughput screening or multi-temperature crystallography could therefore augment the structure-based drug design toolbox.
Idiosyncratic, retinotopic bias in face identification modulated by familiarity
Authors: di Oleggio Castello Matteo Visconti , Taylor Morgan , Cavanagh Patrick , Ida Gobbini M.
Published: January 2018

The perception of gender and age of unfamiliar faces is reported to vary idiosyncratically across retinal locations such that, for example, the same androgynous face may appear to be male at one location but female at another. Here we test spatial heterogeneity for the recognition of theidentityof personally familiar faces in human participants. We found idiosyncratic biases that were stable within participants and that varied more across locations for low as compared to high familiar faces. These data suggest that like face gender and age, face identity is processed, in part, by independent populations of neurons monitoring restricted spatial regions and that the recognition responses vary for the same face across these different locations. Moreover, repeated and varied social interactions appear to lead to adjustments of these independent face recognition neurons so that the same familiar face is eventually more likely to elicit the same recognition response across widely separated visual field locations. We provide a mechanistic account of this reduced retinotopic bias based on computational simulations.

Significance statement

In this work we tested spatial heterogeneity for the recognition of personally familiar faces. We found retinotopic biases that varied more across locations for low as compared to highly familiar faces. The retinotopic biases were idiosyncratic and stable within participants. Our data suggest that, like face gender and age, face identity is processed by independent populations of neurons monitoring restricted spatial regions and that recognition may vary for the same face at these different locations. Unlike previous findings, our data and computational simulation address the effects of learning and show how increased familiarity modifies the representation of face identity in face-responsive cortical areas. This new perspective has broader implications for understanding how learning optimizes visual processes for socially salient stimuli.
Priority effects and non-hierarchical competition shape species composition in a complex grassland community
Authors: Uricchio Lawrence H. , Daws S. Caroline , Spear Erin R. , Mordecai Erin A.
Published: January 2018

Niche and fitness differences control the outcome of competition, but determining their relative importance in invaded communities – which may be far from equilibrium – remains a pressing concern. Moreover, it is unclear whether classic approaches for studying competition, which were developed predominantly for pairs of interacting species, will fully capture dynamics in complex species assemblages. We parameterized a population dynamic model using competition experiments of two native and three exotic species from a grassland community. We found evidence for minimal fitness differences or niche differences between the native species, leading to slow replacement dynamics and priority effects, but large fitness advantages allowed exotics to unconditionally invade natives. Priority effects driven by strong interspecific competition between exotic species drove single-species dominance by one of two exotic species in 80% of model outcomes, while a complex mixture of non-hierarchical competition and coexistence between native and exotic species occurred in the remaining 20%. Fungal infection, a commonly hypothesized coexistence mechanism, had weak fitness effects, and is unlikely to substantially affect coexistence. In contrast to previous work on pairwise outcomes in largely native-dominated communities, our work supports a role for nearly-neutral dynamics and priority effects as drivers of species composition in invaded communities.
A MinION-based pipeline for fast and cost-effective DNA barcoding
Authors: Srivathsan Amrita , Baloğlu Bilgenur , Wang Wendy , Tan Wei Xin , Bertrand Denis , Ng Amanda Hui Qi , Boey Esther Jia Hui , Koh Jayce Jia Yu , Nagarajan Niranjan , Meier Rudolf
Published: January 2018

DNA barcodes are useful for species discovery and species identification, but obtaining barcodes currently requires a well-equipped molecular laboratory, is time-consuming, and/or expensive. We here address these issues by developing a barcoding pipeline for Oxford Nanopore MinION™ and demonstrate that one flowcell can generate barcodes for ∼500 specimens despite high base-call error rates of MinION™. The pipeline overcomes the errors by first summarizing all reads for the same tagged amplicon as a consensus barcode. These barcodes are overall mismatch-free but retain indel errors that are concentrated in homopolymeric regions. We thus complement the barcode caller with an optional error correction pipeline that uses conserved amino-acid motifs from publicly available barcodes to correct the indel errors. The effectiveness of this pipeline is documented by analysing reads from three MinION™ runs that represent three different stages of MinION™ development. They generated data for (1) 511 specimens of a mixed Diptera sample, (2) 575 specimens of ants, and (3) 50 specimens of Chironomidae. The run based on the latest chemistry yielded MinION barcodes for 490 specimens which were assessed against reference Sanger barcodes (N=471). Overall, the MinION barcodes have an accuracy of 99.3%-100% and the number of ambiguities ranges from <0.01-1.5% depending on which correction pipeline is used. We demonstrate that it requires only 2 hours of sequencing to gather all information that is needed for obtaining reliable barcodes for most specimens (>90%). We estimate that up to 1000 barcodes can be generated in one flowcell and that the cost of a MinION barcode can be <USD 2.
Dynamic combination of sensory and reward information under time pressure
Authors: Farashahi Shiva , Ting Chih-Chung , Kao Chang-Hao , Wu Shih-Wei , Soltani Alireza
Published: January 2018

When making choices, collecting more information is beneficial but comes at the cost of sacrificing time that could be allocated to making other potentially rewarding decisions. To investigate how the brain balances these costs and benefits, we conducted a series of novel experiments in humans and simulated various computational models. Under six levels of time pressure, subjects made decisions either by integrating sensory information over time or by dynamically combining sensory and reward information over time. We found that during sensory integration, time pressure reduced performance as the deadline approached, and choice was more strongly influenced by the most recent sensory evidence. By fitting performance and reaction time with various models we found that our experimental results are more compatible with leaky integration of sensory information with an urgency signal or a decision process based on stochastic transitions between discrete states modulated by an urgency signal. When combining sensory and reward information, subjects spent less time on integration than optimally prescribed when reward decreased slowly over time, and the most recent evidence did not have the maximal influence on choice. The suboptimal pattern of reaction time was partially mitigated in an equivalent control experiment in which sensory integration over time was not required, indicating that the suboptimal response time was influenced by the perception of imperfect sensory integration. Meanwhile, during combination of sensory and reward information, performance did not drop as the deadline approached, and response time was not different between correct and incorrect trials. These results indicate a decision process different from what is involved in the integration of sensory information over time. Together, our results not only reveal limitations in sensory integration over time but also illustrate how these limitations influence dynamic combination of sensory and reward information.
Graphene-oxide quenching-based molecular beacon imaging of exosome-mediated transfer of neurogenic miR-193a on microfluidic platform
Authors: Oh Hyun Jeong , Park Hyejin , Yoon Dayoung , Chung Seok , Hwang Do Won , Lee Dong Soo
Published: January 2018

A microRNA (miR-193a) was found to be transferred in the exosomes of differentiated neural progenitors to undifferentiated clones. Graphene-oxide (GO) quenching-based molecular beacon was developed to detect RNAs in living cells and tissues quickly and sensitively. Here, we applied GO quencher-based molecular beacon sensor to visualize neurogenic miR-193a levels delivered via exosome during cell-non-autonomous neurogenesis of neural progenitor cells on microfluidic platform. Fluorescence signals of FAM-labeled peptide nucleic acid (PNA) against miR-193a quenched by GO nanosheets (FAM-PNA193a-GO) were recovered in undifferentiated recipient cells differentiated to the neuronal lineage by exosome-mediated neurogenesis 3 days after co-culture with differentiated donor cells. We propose that molecular beacon imaging using PNA-GO complex can be used to visualize individual cellular expression of mature microRNAs revealing their precise spatial localization and temporal sequences by the intercellular exosome delivery of messages to undergo processes such as cell-non-autonomous neurogenesis.
Attention periodically samples competing stimuli during binocular rivalry
Authors: Davidson Matthew James , Alais David , Tsuchiya Naotsugu , van Boxtel Jeroen J.A.
Published: January 2018

The attentional sampling hypothesis suggests that attention rhythmically enhances sensory processing when attending to a single (~8 Hz), or multiple (~4 Hz) objects. Here we investigated using binocular rivalry whether attention samples sensory representations that are not part of the conscious percept, during competition for perceptual dominance. When crossmodally cued toward a conscious image, subsequent changes in consciousness occurred at ~8 Hz, consistent with rates of undivided attentional sampling. However, when attention was cued toward the suppressed image, changes in consciousness slowed to ~3.5 Hz, indicating the division of attention away from the conscious visual image. In the electroencephalogram, we found that at 3.5 and 8 Hz, the strength of inter-trial phase coherence over fronto-temporal and parieto-occipital regions correlated with behavioral measures of changes in perception. When cues were not task-relevant, these effects disappeared, confirming that perceptual changes were dependent upon the allocation of attention, and that attention can flexibly sample away from a conscious image in a task-dependent manner.
Profile of Molecular Subtypes of Breast Cancer Among Bangladeshi Women - Audit of Initial Experience
Authors: Rahman Md. Zillur , Karim Anwarul
Published: January 2018

Background

Receptor status and molecular subtyping of breast cancer are crucial for patient management. We present here our initial experience on the status of different molecular subtypes and clinicopathological characteristics of invasive breast carcinomas in Bangladeshi population especially in Chittagong zone.

Materials and methods

A total of 59 histopathologically confirmed cases of invasive ductal carcinoma were selected for this study. Fifteen out of 59 cases were reported as HER2 equivalent and could not be categorized into any subtype because of the lack of availability of fluorescence in situ hybridization. The remaining 44 cases were distributed into different molecular subtypes and then the clinicopathological characteristics were compared for each molecular subtype.

Results

Age ranges from 24-70 years with a mean age of 43.95 years. Most of the patients were in 41-50 years age group. Among the 44 cases, most common subtype was HER2/neu amplification (13 cases, 29.55%). Luminal A, luminal B and basal like subtypes were 11 (25%), 10 (22.73%) and 10 (22.73%) respectively. The mean tumor size was 3.46 cm and the highest mean tumor size was in basal-like subtype (4.01cm). Twenty five out of 59 cases (42.37%) showed axillary lymph node metastasis. Lowest axillary lymph node metastasis was found in luminal A subtype (3/11=27.27%).

Conclusion

HER2/neu amplification subtype was found to be more common in this region. Luminal A subtype was found to be more favorable in comparison to the other subtypes in terms of axillary lymph node metastasis.
Meta-analyses identify differentially expressed microRNAs in Parkinson’s disease
Authors: Schulz Jessica , Takousis Petros , Wohlers Inken , Itua Ivie O G , Dobricic Valerija , Rücker Gerta , Binder Harald , Middleton Lefkos , Ioannidis John P A , Perneczky Robert , Bertram Lars , Lill Christina M
Published: January 2018

Objective

MicroRNA-mediated (dys)regulation of gene expression has been implicated in Parkinson’s disease (PD), although results of microRNA expression studies remain inconclusive. We aimed to identify microRNAs that show consistent differential expression across all published expression studies in PD.

Methods

We performed a systematic literature search on microRNA expression studies in PD and extracted data from eligible publications. After stratification for brain, blood, and cerebrospinal fluid (CSF)-derived specimen we performed meta-analyses across microRNAs assessed in three or more independent datasets. Meta-analyses were performed using effect-size and p-value based methods, as applicable.

Results

After screening 599 publications we identified 47 datasets eligible for meta-analysis. On these, we performed 160 meta-analyses on microRNAs quantified in brain (n=125), blood (n=31), or CSF samples (n=4). Twenty-one meta-analyses were performed using effect sizes. We identified 13 significantly (Bonferroni-adjusted α=3.13×10-4) differentially expressed microRNAs in brain (n=3) and blood (n=10) with consistent effect directions across studies. The most compelling findings were with hsa-miR-132-3p (p=6.37×10-5), hsa-miR-497-5p (p=1.35×10-4), and hsa-miR-133b (p=1.90×10-4) in brain, and with hsa-miR-221-3p (p=4.49×10-35), hsa-miR-214-3p (p=2.00×10-34), and hsa-miR-29c-3p (p=3.00×10-12) in blood. No significant signals were found in CSF. Analyses of GWAS data for target genes of brain microRNAs showed significant association (α=9.40×10-5) of genetic variants in nine loci.

Interpretation

We identified several microRNAs that showed highly significant differential expression in PD. Future studies may assess the possible role of the identified brain miRNAs in pathogenesis and disease progression as well as the potential of the top blood microRNAs as biomarkers for diagnosis, progression or prediction of PD.
Seasonal plasticity in anti-predatory strategies: matching of color and color preference for effective crypsis
Authors: van Bergen Erik , Beldade Patricia
Published: January 2018

Effective anti-predatory strategies typically require matching appearance and behavior in prey, and there are many compelling examples of behavioral repertoires that enhance the effectiveness of morphological defenses. When protective adult morphology is induced by developmental environmental conditions predictive of future predation risk, adult behavior should be adjusted accordingly to maximize predator avoidance. While behavior is typically strongly affected by the adult environment, developmental plasticity in adult behavior - mediated by the same pre-adult environmental cues that affect morphology - could ensure an effective match between anti-predatory morphology and behavior. The coordination of environmentally-induced responses may be especially important in populations exposed to predictable environmental fluctuations (e.g. seasonality). Here, we studied early and late life environmental effects on a suite of traits expected to work together for effective crypsis. We focused on wing color and background color preference in Bicyclus anynana, a model of developmental plasticity that relies on crypsis as a seasonal strategy for predator avoidance. Using a full-factorial design, we disentangled effects of developmental and adult ambient temperature on both appearance and behavior. We showed that developmental conditions affect both adult color and color preference, with temperatures that simulate natural dry season conditions leading to browner butterflies with a perching preference for brown backgrounds. This effect was stronger in females, especially when butterflies were tested at lower ambient temperatures. In contrast to the expectation that motionlessness enhances crypsis, we found no support for our hypothesis that the browner dry-season butterflies would be less active. We argue that the integration of developmental plasticity for morphological and behavioral traits might improve the effectiveness of seasonal anti-predatory strategies.
Understanding the role of alterations in cortical D1 receptor sensitivity in shaping working memory maintenance through mesocortical dynamics
Authors: Reneaux Melissa , Gupta Rahul
Published: January 2018

The dopamine (DA) hypothesis of cognitive deficits suggests that too low or too high extracellular DA concentration in the prefrontal cortex (PFC) can severely impair the working memory (WM) maintenance during delay period. Thus, there exists only an optimal range of DA where the sustained-firing activity, the neural correlate of WM maintenance, in the cortex possesses optimal firing frequency as well as robustness against noisy distractions. Empirical evidences demonstrate changes even in the D1 receptor (D1R)-sensitivity to extracellular DA, collectively manifested through D1R density and DA-binding affinity, in the PFC under neuropsychiatric conditions such as ageing and schizophrenia. However, the impact of alterations in the cortical D1R-sensitivity on WM maintenance has yet remained poorly addressed. Using a quantitative neural mass model of the prefronto-mesoprefrontal system, the present study reveals that higher D1R-sensitivity may not only effectuate shrunk optimal DA range but also shift of the range to lower concentrations. Moreover, higher sensitivity may significantly reduce the WM-robustness even within the optimal DA range and exacerbates the decline at abnormal DA levels. These findings project important clinical implications, such as dosage precision and variability of DA-correcting drugs across patients, and failure in acquiring healthy WM maintenance even under drug-controlled normal cortical DA levels.
Dissecting dynamics and differences of selective pressures in the evolution of human pigmentation
Authors: Huang Xin , He Yungang , Wang Sijia , Jin Li
Published: January 2018

Human pigmentation is a highly diverse and complex trait among populations, and has drawn particular attention from both academic and non-academic investigators for thousands of years. Previous studies detected selection signals in several human pigmentation genes, but few studies have integrated contribution from multiple genes to the evolution of human pigmentation. Moreover, none has quantified selective pressures on human pigmentation over epochs and between populations. Here, we dissect dynamics and differences of selective pressures during different periods and between distinct populations with new approaches. We propose a new model with multiple populations to estimate historical selective pressures by summarizing selective pressures on multiple genes. We use genotype data of 19 genes associated with human pigmentation from 17 datasets, and obtain data for 2346 individuals of six representative population groups from worldwide. Our results quantify selective pressures on light pigmentation not only in modern Europeans (0.0249/generation) but also in proto-Eurasians (0.00665/generation). Our results also support several derived alleles associated with human dark pigmentation may under directional selection by quantifying differences of selective pressures between populations. Our study provides a first attempt to quantitatively investigate the dynamics of selective pressures during different time periods in the evolution of human pigmentation, and may facilitate studies of the evolution of other complex traits.

Author Summary

The color variation of human skin, hair, and eye is affected by multiple genes with different roles. This diversity may be shaped by natural selection and adapted for ultraviolet radiation in different environments around the world. As human populations migrated out from Africa, the ultraviolet radiation in the environment they encountered also changed. It is possible that the selective pressures on human pigmentation varied throughout human evolutionary history. In this study, we develop a new approach and estimate historical selective pressures on light pigmentation not only in modern Europeans but also in proto-Eurasians. To our best knowledge, this is the first study that quantifies selective pressures during different time periods in the evolution of human pigmentation. Besides, we provide statistical evidence to support several genes associated with human dark pigmentation may be favored by natural selection. Thus, natural selection may not only affect light pigmentation in Eurasians, but also influence dark pigmentation in Africans.
Parametric and Non-parametric Gradient Matching for Network Inference
Authors: Dony Leander , He Fei , Stumpf Michael PH
Published: January 2018

Reverse engineering of gene regulatory networks from time series gene-expression data is a challenging problem, not only because of the vast sets of candidate interactions but also due to the stochastic nature of gene expression. To avoid the computational cost of large-scale simulations, a two-step Gaussian process interpolation based gradient matching approach has been proposed to solve differential equations approximately. Based on this gradient matching approach, we evaluate the fits of parametric as well as non-parametric candidate models to the data under various settings for different inference objectives. We also use model averaging, based on the Bayesian Information Criterion (BIC), in order to combine the different inferences. We found that parametric methods can provide comparable, and often improved inference compared to non-parametric methods; the latter, however, require no kinetic information and are computationally more efficient.

The code used in this work is available athttps://github.com/ld2113/Final-Project.
Genome-wide analysis of consistently RNA edited sites in human blood reveals interactions with mRNA processing genes and suggests correlations with cell types and biological variables
Authors: Giacopuzzi Edoardo , Gennarelli Massimo , Sacco Chiara , Filippini Alice , Mingardi Jessica , Magri Chiara , Barbon Alessandro
Published: January 2018

Background

A-to-I RNA editing is a co-/post-transcriptional modification catalyzed by ADAR enzymes, that deaminates Adenosines (A) into Inosines (I). Most of known editing events are located within inverted ALU repeats, but they also occur in coding sequences and may alter the function of encoded proteins. RNA editing contributes to generate transcriptomic diversity and it is found altered in cancer, autoimmune and neurological disorders. Emerging evidences indicate that editing process could be influenced by genetic variations, biological and environmental variables.

Results

We analyzed RNA editing levels in human blood using RNA-seq data from 459 healthy individuals and identified 2,079 sites consistently edited in this tissue. As expected, analysis of gene expression revealed thatADARis the major contributor to editing on these sites, explaining ∼13% of observed variability. After removingADAReffect, we found significant associations for 1,122 genes, mainly involved in RNA processing. These genes were significantly enriched in genes encoding proteins interacting with ADARs, including 276 potential ADARs interactors and 9 ADARs direct partners. In addition, our analysis revealed several factors potentially influencing RNA editing in blood, including cell composition, age, Body Mass Index, smoke and alcohol consumption. Finally, we identified genetic loci associated with editing levels, including knownADAReQTLs and a small region on chromosome 7, containingLOC730338,a lincRNA gene that appears to modulate ADARs mRNA expression.

Conclusions

Our data provides a detailed picture of the most relevant RNA editing events and their variability in human blood, giving interesting insights on potential mechanisms behind this post-transcriptional modification and its regulation in this tissue.
Deciphering noise amplification and reduction in open chemical reaction networks
Authors: Pucci Fabrizio , Rooman Marianne
Published: January 2018

The impact of fluctuations on the dynamical behavior of complex biological systems is a longstanding issue, whose understanding would elucidate how evolutionary pressure tends to modulate intrinsic noise. Using the Itō stochastic differential equation formalism, we performed analytic and numerical analyses of model systems containing different molecular species in contact with the environment and interacting with each other through mass-action kinetics. For networks of zero deficiency, which admit a detailed- or complex-balanced steady state, all molecular species are uncorrelated and their Fano factors are Poissonian. Systems of higher deficiency have non-equilibrium steady states and non-zero reaction fluxes flowing between the complexes. When they model homooligomerization, the noise on each species is reduced when the flux flows from the oligomers of lowest to highest degree, and amplified otherwise. In the case of hetero-oligomerization systems, only the noise on the highest-degree species shows this behavior.
Triple Representation of Language, Working Memory, Social and Emotion Processing in the Cerebellum: Convergent Evidence from Task and Seed-Based Resting-State Fmri Analyses in a Single Large Cohort
Authors: Guell Xavier , Gabrieli John D.E. , Schmahmann Jeremy D.
Published: January 2018

Delineation of functional topography is critical to the evolving understanding of the cerebellum’s role in a wide range of nervous system functions. We used data from the Human Connectome Project (n=787) to analyze cerebellar fMRI task activation (motor, working memory, language, social and emotion processing) and resting-state functional connectivity calculated from cerebral cortical seeds corresponding to the peak Cohen’s d of each task contrast. The combination of exceptional statistical power, activation from both motor and multiple non-motor tasks in the same participants, and convergent resting-state networks in the same participants revealed novel aspects of the functional topography of the human cerebellum. Consistent with prior studies there were two distinct representations of motor activation. Newly revealed were three distinct representations each for working memory, language, social, and emotional task processing that were largely separate for these four cognitive and affective domains. In most cases, the task-based activations and the corresponding resting-network correlations were congruent in identifying the two motor representations and the three non-motor representations that were unique to working memory, language, social cognition, and emotion. The definitive localization and characterization of distinct triple representations for cognition and emotion task processing in the cerebellum opens up new basic science questions as to why there are triple representations (what different functions are enabled by the different representations?) and new clinical questions (what are the differing consequences of lesions to the different representations?).

HIGHLIGHTS

-

We analyzed motor and multiple nonmotor task fMRI activations in the cerebellum.

-

Resting-state seeds were placed at each task activation peak in the cerebral cortex.

-

We describe cerebellar task topography in the largest single cohort studied to date.

-

Nonmotor cerebellar task activation revealed a pattern of triple representation.

-

Resting-state analysis revealed an overlapping pattern of triple representation.
The yeast GRASP Grh1 displays a high polypeptide backbone mobility along with an amyloidogenic behavior
Authors: Fontana N. A. , Fonseca-Maldonado R. , Mendes L.F.S , Meleiro L. P. , Costa-Filho A. J.
Published: January 2018

GRASPs are proteins involved in cell processes that seem paradoxical, such as being responsible for shaping the Golgi cisternae and also involved in unconventional secretion mechanisms that bypass the Golgi, among other functions in the cell. Despite its involvement in several relevant cell processes, there is still a considerable lack of studies on full-length GRASPs. Our group has previously reported an unexpected behavior of the full-length GRASP from the fungus C. neoformans: its intrinsically-disordered characteristic. Here, we generalize this finding by showing that is also observed in the GRASP from the yeast S. cerevisae (Grh1), which strongly suggests it may be a general property within the GRASP family. Furthermore, Grh1 is also able to form amyloid fibrils either upon heating or when submitted to changes in the dielectric constant of its surroundings, a condition that is experienced by the protein when in close contact with membranes of cell compartments, such as the Golgi apparatus. Intrinsic disorder and amyloid fibril formation can thus be two structural properties exploited by GRASP during its functional cycle.
Whole genome sequence of an edible and potential medicinal fungus, Cordyceps guangdongensis
Authors: Zhang Chenghua , Deng Wangqiu , Yan Wenjuan , Li Taihui
Published: January 2018

Cordyceps guangdongensis is an edible fungus which has been approved as a Novel Food by the Chinese Ministry of Public Health in 2013. It also has a broad application prospect in pharmaceutical industries with many medicinal activities. In this study, the whole genome of C. guangdongensis GD15, a single spore isolate from a wild strain, was sequenced and assembled with Illumina and PacBio sequencing technology. The generated genome is 29.05 Mb in size, comprising 9 scaffolds with an average GC content of 57.01%. It is predicted to contain a total of 9150 protein-coding genes. Sequence identification and comparative analysis indicated that the assembled scaffolds contained two complete chromosomes and four single-end chromosomes, showing a high level assembly. Gene annotation revealed a diversity of transporters that could contribute to the genome size and evolution. Besides, approximately 15.49% and 13.70% genes involved in metabolic processes were annotated by KEGG and COG respectively. Genes belonging to CAZymes accounted for a proportion of 2.84% of the total genes. In addition, 435 transcription factors (TFs) were identified, which were involved in various biological processes. Among the identified TFs, the fungal transcription regulatory proteins (18.39%) and fungal-specific TFs (19.77%) represented the two largest classes of TFs. These data provided a much needed genomic resource for studying C. guangdongensis, laying a solid foundation for further genetic and biological studies, especially for elucidating the genome evolution and exploring the regulatory mechanism of fruiting body development.