bluuebunny/crossref_metadata_2025 huggingface dataset:
Distance to white matter trajectories is associated with treatment response to internal capsule deep brain stimulation in treatment-resistant depression
Authors: Liebrand Luka C. , Natarajan Samuel J. , Caan Matthan W.A. , Schuurman P. Rick , van den Munckhof Pepijn , de Kwaasteniet Bart , Luigjes Judy , Bergfeld Isidoor O. , Denys Damiaan , van Wingen Guido A.
Published: October 2019

Objective

Deep brain stimulation (DBS) is an innovative treatment for treatment-resistant depression. DBS is usually targeted at specific anatomical landmarks, with patients responding to DBS in approximately 50% of cases. Attention has recently shifted to white matter tracts to explain DBS response, with initial open-label trials targeting white matter tracts yielding much higher response rates (>70%).

Methods

We associated distance to individual white matter tracts around the stimulation target in the ventral anterior limb of the internal capsule to treatment response. We performed diffusion magnetic resonance tractography of the superolateral branch of the medial forebrain bundle and the anterior thalamic radiation in fourteen patients that participated in our randomized clinical trial. We combined the tract reconstructions with the postoperative images to identify the DBS leads and estimated the distance between tracts and leads, which we subsequently associated with treatment response.

Results

Stimulation closer to both tracts was significantly correlated to a larger symptom decrease (r=0.61, p=0.02), suggesting that stimulation more proximal to the tracts was beneficial. There was no difference in lead placement with respect to anatomical landmarks, which could mean that differences in treatment response were driven by individual differences in white matter anatomy.

Conclusions

Our results suggest that deep brain stimulation of the ventral anterior limb of the internal capsule could benefit from targeting white matter bundles. We recommend acquiring diffusion magnetic resonance data for each individual patient.
Identification of newborns at risk for autism using electronic medical records and machine learning
Authors: Rahman Rayees , Kodesh Arad , Levine Stephen Z , Sandin Sven , Reichenberg Abraham , Schlessinger Avner
Published: October 2019

Importance

Current approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, where most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and outcome.

Objective

Develop a machine learning (ML) method predicting the diagnosis of ASD in offspring in a general population sample, using parental electronic medical records (EMR) available before childbirth

Design

Prognostic study of EMR data within a single Israeli health maintenance organization, for the parents of 1,397 ASD children (ICD-9/10), and 94,741 non-ASD children born between January 1st, 1997 through December 31st, 2008. The complete EMR record of the parents was used to develop various ML models to predict the risk of having a child with ASD.

Main outcomes and measures

Routinely available parental sociodemographic information, medical histories and prescribed medications data until offspring’s birth were used to generate features to train various machine learning algorithms, including multivariate logistic regression, artificial neural networks, and random forest. Prediction performance was evaluated with 10-fold cross validation, by computing C statistics, sensitivity, specificity, accuracy, false positive rate, and precision (positive predictive value, PPV).

Results

All ML models tested had similar performance, achieving an average C statistics of 0.70, sensitivity of 28.63%, specificity of 98.62%, accuracy of 96.05%, false positive rate of 1.37%, and positive predictive value of 45.85% for predicting ASD in this dataset.

Conclusion and relevance

ML algorithms combined with EMR capture early life ASD risk. Such approaches may be able to enhance the ability for accurate and efficient early detection of ASD in large populations of children.

Key points

Question

Can autism risk in children be predicted using the pre-birth electronic medical record (EMR) of the parents?

Findings

In this population-based study that included 1,397 children with autism spectrum disorder (ASD) and 94,741 non-ASD children, we developed a machine learning classifier for predicting the likelihood of childhood diagnosis of ASD with an average C statistic of 0.70, sensitivity of 28.63%, specificity of 98.62%, accuracy of 96.05%, false positive rate of 1.37%, and positive predictive value of 45.85%.

Meaning

The results presented serve as a proof-of-principle of the potential utility of EMR for the identification of a large proportion of future children at a high-risk of ASD.
Memory recovery is related to default mode network impairment and neurite density during brain tumours treatment
Authors: Romero-Garcia Rafael , Suckling John , Owen Mallory , Assem Moataz , Sinha Rohitashwa , Coelho Pedro , Woodberry Emma , Price Stephen J , Burke Amos , Santarius Thomas , Erez Yaara , Hart Michael
Published: October 2019

Objective

The aim of this study is to test brain tumour interactions with brain networks thereby identifying protective features and risk factors for memory recovery after surgical resection.

Methods

Seventeen patients with diffuse non-enhancing glioma (aged 22-56 years) were longitudinally MRI-scanned before and after surgery, and during a 12-months recovery period (47 MRI in total after exclusion). After each scanning session, a battery of memory tests was performed using a tablet-based screening tool, including free verbal memory, overall verbal memory, episodic memory, orientation, forward digit span and backwards digit span. Using structural MRI and Neurite Orientation Dispersion and Density Imaging (NODDI) derived from diffusion-weighted images, we respectively estimated lesion overlap and Neurite Density with brain networks derived from normative data in healthy participants (somato-motor, dorsal attention, ventral attention, fronto-parietal and Default Mode Network -DMN-). Linear Mixed Models (LMMs) that regressed out the effect of age, gender, tumour grade, type of treatment, total lesion volume and total neurite density were used to test the potential longitudinal associations between imaging markers and memory recovery.

Results

Memory recovery was not significantly associated with tumour location based on traditional lobe classification nor with the type of treatment received by patients (i.e. surgery alone or surgery with adjuvant chemoradiotherapy). Non-local effects of tumours were evident on Neurite Density, which was reduced not only within the tumour, but also beyond the tumour boundary. In contrast, high preoperative Neurite Density outside the tumour, but within the DMN, was associated with better memory recovery (LMM, Pfdr<10−3). Furthermore, postoperative and follow-up Neurite Density within the DMN and fronto-parietal network were also associated with memory recovery (LMM, Pfdr=0.014 and Pfdr=0.001, respectively). Preoperative tumour, and post-operative lesion, overlap with the DMN showed a significant negative association with memory recovery (LMM, Pfdr=0.002 and Pfdr<10−4, respectively).

Conclusion

Imaging biomarkers of cognitive recovery and decline can be identified using NODDI and resting-state networks. Brain tumours and their corresponding treatment affecting brain networks that are fundamental for memory functioning such as the DMN can have a major impact on patient’s memory recovery.
Eye contact in active and passive viewing: event-related brain potential evidence from a combined eye tracking and EEG study
Authors: Stephani T. , Kirk Driller K. , Dimigen O. , Sommer W.
Published: October 2019

Eye contact is a salient social cue which is assumed to influence early brain processes involved in face perception. The N170 component in the event-related potential (ERP) has frequently been reported to be larger to faces with an averted rather than direct gaze towards the observer. In most studies, however, this effect has been investigated in comparatively artificial, passive settings where participants were instructed to fixate their gaze while observing occasional gaze changes in stimulus faces. Yet, it is unclear whether similar mechanisms are in place during naturalistic gaze interactions involving the continuous interplay of directed and averted gaze between the communication partners. To fill this gap, we compared passive viewing of gaze change sequences with an active condition where participants’ own gaze continuously interacted with the gaze of a stimulus face; while recording ERPs and monitoring gaze with eye tracking. In addition, we investigated the relevance of emotional facial expressions for gaze processing. For both passive viewing and active interaction, N170 amplitudes were larger when the gaze of stimulus faces was averted rather than directed at the participants. Furthermore, eye contact decreased P300 amplitudes in both conditions. Emotional facial expression influenced N170 amplitudes but did not elicit an early posterior negativity nor did it interact with gaze direction. We conclude that comparable mechanisms of gaze perception are in place in gaze interaction as compared to passive viewing, encouraging the further study of the eye contact effect in naturalistic settings.
Sub-species niche specialization in the oral microbiome is associated with nasopharyngeal carcinoma risk
Authors: Debelius Justine W. , Huang Tingting , Cai Yonglin , Ploner Alexander , Barrett Donal , Zhou Xiaoying , Xiao Xue , Li Yancheng , Liao Jian , Zheng Yuming , Huang Guangwu , Adami Hans-Olov , Zeng Yi , Zhang Zhe , Ye Weimin
Published: October 2019

Oral health and changes in the oral microbiome have been associated with both local and systemic cancer. Poor oral hygiene is a known risk factor for Nasopharyngeal Carcinoma (NPC), a virally-associated head and neck cancer endemic to southern China. We explored the relationship between NPC and the oral microbiome using 16s rRNA sequencing in a study of 499 NPC patients and 495 population-based age and sex frequency-matched controls from an endemic area of Southern China. We found a significant reduction in community richness in cases compared to controls. Differences in the overall microbial community structure between cases and controls could not be explained by other potential confounders; disease status explained 5 times more variation in the Unweighted UniFrac distance than the next most explanatory variable. In feature-based analyses, we identified a pair of co-excludingGranulicatella adiacens(G. adicans) amplicon sequence variants (ASVs) which were strongly associated with NPC status and differed by a single nucleotide. TheG. adicansvariant an individual carried was also associated with the overall microbial community based on beta diversity. Co-occurrence analysis suggested the twoG. adicansASVs sit at the center of two co-excluding clusters of closely related organisms. Our results suggest there are differences in the oral microbiome between NPC patients and healthy controls and these may be associated with both a loss of microbial diversity and niche specialization among closely related commensals.

Importance

The relationship between oral health and the risk of Nasopharyngeal Carcinoma has been previously established. However, the role of oral microbiome has not been evaluated in the disease in a large epidemiological study. This paper clearly establishes a difference in the oral microbiome between NPC patients and healthy controls which cannot be explained by other confounding factors. It furthermore identifies a pair of closely related co-excluding organisms associated with the disease, highlighting the importance of modern methods for single nucleotide resolution in 16s rRNA sequence characterization. To the best of our knowledge, this is one of the first examples of cancer-associated niche-specialization of the oral microbiome.
Finding the neural correlates of collaboration using a three-person fMRI hyperscanning paradigm
Authors: Xie Hua , Howell Amber , Schreier Meredith , Sheau Kristen E. , Manchanda Mai K. , Ayub Rafi , Glover Gary , Jung Malte , Reiss Allan L. , Saggar Manish
Published: October 2019

Humans have an extraordinary ability to interact and cooperate with others, which plays a pivotal role in societies at large. Despite its potential social and evolutionary significance, research on finding the neural correlates of collaboration has been limited partly due to restrictions on simultaneous neuroimaging of more than one participant (a.k.a. hyperscanning). A series of works now exists that used dyadic fMRI hyperscanning to examine the interaction between two participants. However, to our knowledge, no study to date has aimed at revealing the neural correlates of social interactions using a 3-person (or triadic) fMRI hyperscanning paradigm. Here, for the first time, we simultaneously measured the blood-oxygenation-level-dependent (BOLD) signal of triads (m=12 triads; n=36 participants), while they engaged in a joint drawing task based on the social game of Pictionary®. General linear model (GLM) analysis revealed increased activation in the brain regions previously linked with the theory of mind (ToM) during the collaborative phase compared to the independent phase of the task. Furthermore, using intersubject brain synchronization (IBS) analysis, we revealed increased synchrony of the right temporo-parietal junction (R TPJ) during the collaborative phase. The increased synchrony in the R TPJ was observed to be positively associated with the overall team performance on the task. In sum, our novel paradigm revealed a vital role of the R TPJ among other ToM regions during a triadic collaborative drawing task.
Semantic Reversal Anomalies under the Microscope: Task and Modality Influences on Language-Associated Event-Related Potentials
Authors: Kyriaki Louise , Schlesewsky Matthias , Bornkessel-Schlesewsky Ina
Published: October 2019

Semantic reversal anomalies (SRAs) – sentences where an implausibility is created by reversing participant roles – have attracted much attention in the literature on the electrophysiology of language. In spite of being syntactically well-formed but semantically implausible, these sentences unexpectedly elicited a monophasic P600 effect in English and Dutch rather than an N400 effect. Subsequent research revealed variability in the presence/absence of an N400 effect to SRAs depending on the language examined and the choice of verb type in English. However, most previous studies employed the same presentation modality (visual) and task (acceptability judgement). Here, we conducted two experiments and three statistical analyses to investigate the influence of stimulus modality, task demand, and statistical choices on event-related potential (ERP) response patterns to SRAs in English. We reproduced a previous study’s procedure and analysis (Bourguignon et al., 2012), and further introduced between-subjects factors of task type and modality, using mixed effects modelling to analyse the data. We observed an N400 effect to typical English SRAs (agent subject verbs, e.g. the fries will eat the boys), which contrasts existing literature and was not predicted by existing theories that account for SRA processing. Task demand modulated the ERPs elicited by SRAs, while auditory presentation led to increased comprehension accuracy and a more broadly distributed ERP. Finally, the statistical methods used influenced the presence/absence of ERP effects. Our results suggest a sensitivity of language-related ERP patterns to methodological parameters and we conclude that future experiments should take this into careful consideration.
Light exposure decreases infectivity of theDaphniaparasitePasteuria ramosa
Authors: Overholt Erin P. , Duffy Meghan A. , Meeks Matthew P. , Leach Taylor H. , Williamson Craig E.
Published: October 2019

Climate change is altering light regimes in lakes, which should impact disease outbreaks, since sunlight can harm aquatic pathogens. However, some bacterial endospores are resistant to damage from light, even surviving exposure to UV-C. We examined the sensitivity ofPasteuria ramosaendospores, an aquatic parasite infectingDaphniazooplankton, to biologically relevant wavelengths of light. Laboratory exposure to increasing intensities of UV-B, UV-A, and visible light significantly decreasedP. ramosainfectivity, though there was no effect of spore exposure on parasitic castration of the host.P. ramosais more sensitive than itsDaphniahost to damage by longer wavelength UV-A and visible light; this may enableDaphniato seek an optimal light environment in the water column where both UV-B damage and parasitism are minimal. Studies of pathogen light sensitivity help us uncover factors controlling epidemics in lakes, which is especially important given that water transparency is decreasing in many lakes.
Phenylethynylbenzyl-Modified Biguanides Inhibit Pancreatic Cancer Tumor Growth
Authors: Hébert Audrey , Parisotto Maxime , Rowell Marie-Camille , Doré Alexandra , Fernandez Ana , Lefrancois Guillaume , Kalegari Paloma , Ferbeyre Gerardo , Schmitzer Andreea R.
Published: October 2019

We present the design and synthesis of a small library of substituted biguanidium salts and their capacity to inhibit the growth/viability of pancreatic cancer cells. We first present their in vitro and membrane activity, before we address their mechanism of action in living cells and in vivo activity. We show that phenylethynyl biguanidium salts possess higher ability to cross hydrophobic barriers, improved mitochondrial accumulation and anticancer activity. Mechanistically, the most active compound 1b, like metformin, decreases the NAD+/NADH ratio and mitochondrial respiration, but at 800-fold lower concentration. In vivo studies with, the most active, compound 1b show a significant growth inhibition of pancreatic cancer xenografts in mice, while biguanides currently in clinical trials had no activity.
The norepinephrine transporter regulates dopamine-dependent synaptic plasticity in the mouse dorsal hippocampus
Authors: Sonneborn Alex , Greene Robert W.
Published: October 2019

The rodent dorsal hippocampus is essential for episodic memory consolidation, a process dependent on dopamine D1-like receptor activation. It was previously thought that the ventral tegmental area provided the only supply of dopamine to dorsal hippocampus, but several recent studies have established the locus coeruleus (LC) as a second major source. However, the mechanism for LC-dependent dopamine release has never been explored. Our data identify norepinephrine transporter reversal as one plausible mechanism by demonstrating that transporter blockade can reduce dopamine-dependent long-term potentiation in hippocampal slices. We also suggest that presynaptic NMDA receptors on LC terminals may initiate this norepinephrine transporter reversal. Furthermore, as dopamine and norepinephrine should be co-released from the LC, we show that they act together to enhance synaptic strength. Since LC activity is highly correlated with attentional processes and memory, these experiments provide insight into how selective attention influences memory formation at the synaptic and circuit levels.
Evaluating the performance of malaria genomics for inferring changes in transmission intensity using transmission modelling
Authors: Watson Oliver J. , Okell Lucy C. , Hellewell Joel , Slater Hannah C. , Unwin H. Juliette T. , Omedo Irene , Bejon Philip , Snow Robert W. , Noor Abdisalan M. , Rockett Kirk , Hubbart Christina , Nankabirwa Joaniter I. , Greenhouse Bryan , Chang Hsiao-Han , Ghani Azra C. , Verity Robert
Published: October 2019

Advances in genetic sequencing and accompanying methodological approaches have resulted in pathogen genetics being used in the control of infectious diseases. To utilise these methodologies for malaria we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment. Here we develop an individual-based transmission model to simulate malaria parasite genetics parameterised using estimated relationships between complexity of infection and age from 5 regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterise the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The best performing model successfully predicted malaria prevalence with mean absolute error of 0.055, suggesting genetic tools could be used for monitoring the impact of malaria interventions.
Chimpanzees use advanced spatial cognition to plan least-cost routes
Authors: Green Samantha J. , Boruff Bryan J. , Grueter Cyril C.
Published: October 2019

While the ability of naturally ranging animals to recall the location of food resources and use straight-line routes between them has been demonstrated in several studies, it is not known whether animals can use knowledge of their physical landscape to plan least-cost routes. This ability is likely to be particularly important for animals living in highly variable energy landscapes, where movement costs are exacerbated. Here, we used least-cost modelling to investigate whether chimpanzees (Pan troglodytes) living in a rugged, montane environment use advanced cognitive skills to plan energy efficient routes. We used a subset of chimpanzee movement segments together with the available laboratory measurements of chimpanzee energy expenditure to assign movement ‘costs’ which were incorporated in an anisotropic least-cost model and straight-line null model. The least-cost model performed better than the straight-line model across all parameters, and linear mixed modelling showed a strong relationship between the cost of observed chimpanzee travel and predicted least-cost routes. To our knowledge, our study provides the first example of spatial memory for landscape and the ability to plan least-cost routes in non-human animals. These cognitive abilities may be a key trait that have enabled chimpanzees to maintain their energy balance in a low-resource environment. Our findings provide a further example of how the advanced cognitive complexity of hominids have facilitated their adaptation to a variety of environmental conditions and lead us to hypothesise that landscape complexity may play a role in shaping cognition.
Human gut mobileome during antibiotic therapy. A trajectory-based approach to analysis of the metagenomic time-series datasets
Authors: Górska Anna , Schlaberg Robert , Willmann Matthias , Liese Jan , Monjaras Feria Julia Victoria , Wagner Samuel , Autenrieth Ingo , Huson Daniel H. , Peter Silke
Published: October 2019

Motivation

Antibiotic resistance is widely recognized as a severe threat to current medical practice. Each antibiotic therapy drives the emergence and subsequent retention of antibiotics resistance genes within the human gut microbiome. However, the details on how the resistance spreads between bacteria within the human gut remain unknown, as does the role of horizontal gene transfer in this process, too.

Results

We present a novel approach to the analysis of time-series whole-genome metagenomic sequencing data. This involves partitioning the scaffolds from the metagenomic assembly into groups corresponding to bacterial chromosomes, plasmids and those with prophages and transposons. Using specialized sequencing of the bacteriophages we were able to track the flow of ciprofloxacin resistance genes from bacterial chromosomes, through the plasmids, to prophages and phages.

Contact

anna.gorska@univr.it.
UAV Based Imaging Platform for Monitoring Maize Growth Throughout Development
Authors: Tirado Sara B. , Hirsch Candice N. , Springer Nathan M.
Published: October 2019

Plant height (PH) data collected at high temporal resolutions can give insight into important growth parameters useful for identifying elite material in plant breeding programs and developing management guidelines in production settings. However, in order to increase the temporal resolution of PH data collection, more robust, rapid and low-cost methods are needed to evaluate field plots than those currently available. Due to their low cost and high functionality, unmanned aerial vehicles (UAVs) can be an efficient means for collecting height at various stages throughout development. We have developed a procedure for utilizing structure from motion algorithms to collect PH from RGB drone imagery and have used this platform to characterize a yield trial consisting of 24 maize hybrids planted in replicate under two dates and three planting densities in St Paul, MN in the summer of 2018. The field was imaged weekly after planting using a DJI Phantom 4 Advanced drone to extract PH and hand measurements were collected following aerial imaging of the field. In this work, we test the error in UAV PH measurements and compare it to the error obtained within manually acquired PH measurements. We also propose a method for improving the correspondence of manual and UAV measured height and evaluate the utility of using UAV obtained PH data for assessing growth of maize genotypes and for estimating end-season height.
CodAn: predictive models for the characterization of mRNA transcripts in Eukaryotes
Authors: Nachtigall Pedro G , Kashiwabara Andre Y , Durham Alan M
Published: October 2019

Characterization of the coding sequences (CDSs) is an essential step on transcriptome annotation. Incorrect characterization of CDSs can lead to the prediction of non-existent proteins that can eventually compromise knowledge if databases are populated with similar incorrect predictions made in different genomes. Even though some recent methods have succeeded in correctly prediction of the stop codon position in strand-specific sequences, prediction of the complete CDS is still far from a gold standard. More importantly, prediction in strand-blind sequences and in partial sequences is deficient, presenting very low accuracy. Here, we present CodAn, a new computational approach to predict CDS and UTR, that significantly pushes the boundaries of CDS prediction in strand-blind and in partial sequences, increases strand-specific full-CDS predictions and matches or surpasses gold-standard results in strand-specific stop codon predictions. CodAn is freely available for download at https://github.com/pedronachtigall/CodAn.
Regional differences in gene regulation may underlie patterns of sensitivity to novel insecticides in Colorado potato beetle
Authors: Dively Galen P. , Crossley Michael S. , Schoville Sean D. , Steinhauer Nathalie , Hawthorne David J.
Published: October 2019

Agricultural insect pests frequently exhibit geographic variation in levels of insecticide resistance, which are often presumed to be due to the intensity of insecticide use for pest management. However, regional differences in the evolution of resistance to novel insecticides suggests that other factors are influencing rates of adaptation. We examined LC50 bioassay data spanning 15 years and six insecticides (abamectin, imidacloprid, spinosad, cyantraniliprole, chlorantraniliprole, and metaflumizone) for evidence of regional differences in Colorado potato beetle (CPB) baseline sensitivity to insecticides as they became commercially available. We consistently found that CPB populations from the Western USA had the highest baseline sensitivity to novel insecticides, while populations from the Eastern USA had the lowest. Comparisons of gene expression between populations from these regions revealed constitutively elevated expression of an array of detoxification genes in the East, but no evidence of additional induction when exposed to imidacloprid. Our results suggest a mechanism for geographic variation in rates of adaptation to insecticides whereby baseline levels of gene expression determine a population’s response to novel insecticides. These findings have implications for the regional development of insecticide resistance management strategies and for the fundamental question of what determines the rate of adaptation to insecticides.
Diversity and seasonality of horse flies (Diptera: Tabanidae) in Uruguay
Authors: Lucas Martín , Krolow Tiago K. , Riet-Correa Franklin , Barros Antonio Thadeu M. , Krüger Rodrigo F. , Saravia Anderson , Miraballes Cecilia
Published: October 2019

Horse flies (Diptera: Tabanidae) are hematophagous insects that cause direct and indirect losses in livestock production and are important vectors of pathogens. The aim of this study was to determine the diversity and seasonality of horse fly species at an experimental farm in Tacuarembó and the diversity of species in different departments of Uruguay. For 20 months, systematic collections were performed using Nzi and Malaise traps in two different environments at the experimental farm. Temperature, humidity and rainfall were recorded using a local climatological station. In addition, nonsystematic collections were made at farms located in the departments of Paysandú, Tacuarembó and Colonia. A total of 3,666 horse flies were collected, allowing the identification of 16 species. Three species were recorded for the first time in Uruguay:Dasybasis ornatissima(Brèthes),Dasybasis missionum(Macquart), andTabanus aff. platensisBrèthes. A species that had not been previously taxonomically described was identified (Tabanussp.1). In the systematic captures, the most abundant species wereTabanus campestrisBrèthes,T. aff. platensisandD. missionum, representing 77.6% of the collected specimens. The environment was an important factor related to the abundance of horse flies, as well as the mean temperature. The horse fly season in Tacuarembó started in September and ended in May, with three evident peaks, the most important one during summer. No horse flies were caught during winter. Variations in the prevalence of species in the different departments were observed, indicating the need to carry out new sampling efforts in different areas.
Similar network compositions, but distinct neural dynamics underlying belief updating in environments with and without explicit outcomes
Authors: Fiore Vincenzo G. , Gu Xiaosi
Published: October 2019

Classic decision theories, such as reinforcement learning, typically require the presence of explicit outcomes for learning and belief updating. However, ecological environments are often opaque and explicit feedback, such as those based on values, might not be immediately accessible. It remains unclear whether the neural dynamics underlying belief updating in absence of outcomes differ from those responsible for decision-making based on accessible outcomes. Here, we investigated this question in healthy humans (n=28) using Bayesian modeling and two multi-option fMRI tasks, one with and one without immediate outcome. Model-based fMRI analysis revealed two opposing networks encoding belief updating regardless of the presence of immediate outcomes. A “confidence-building” network including the hippocampus, amygdala, and medial prefrontal cortex (mPFC) became more active as beliefs about action-outcome probabilities were confirmed by newly acquired information. Meanwhile, an “uncertainty-building” network including the anterior insular (AIC), dorsal anterior cingulate (dACC), and dorsolateral prefrontal (dlPFC) cortices became more active as new evidence conflicted with action-outcome estimates. Interestingly, dynamic causal modeling revealed that the confidence network was driven either by the hippocampus when outcomes were not available, or by the mPFC and amygdala when value-based outcomes were immediately accessible. Convsersely, the AIC always drove the activities of dACC and dlPFC, under the modulation of increasing uncertainty, independent of outcome availability. These findings reveal similar network compositions but distinct neural dynamics underlying belief updating in changing environments with and without explicit outcomes, highlighting an asymmetric relationship between decision confidence and uncertainty computation across levels of analysis.

Highlights

We investigated belief updating in two tasks, with and without explicit feedback.

Model-based fMRI analysis revealed similar neural responses across tasks.

The anterior insula drove an uncertainty-encoding network, across tasks.

The anterior hippocampus drove a confidence-encoding network, w/o feedbacks.

The medial PFC and amygdala drove a confidence-encoding network, with feedbacks.
Amitosis confers benefits of sex in the absence of sex to Tetrahymena
Authors: Zhang Hao , West Joe A. , Zufall Rebecca A. , Azevedo Ricardo B. R.
Published: October 2019

Sex appears to be the most successful reproductive strategy in eukaryotes despite its many costs. While a complete explanation for sex’s success remains elusive, several evolutionary benefits of sex have been identified. It is predicted that, by forgoing these benefits, asexual lineages are evolutionary dead-ends. Consistent with this prediction, many asexual lineages show signs of accelerated accumulation of deleterious mutations compared to their sexual relatives. Despite these low expectations, some asexual eukaryotic lineages appear to be successful, including the ciliate Tetrahymena. Here, we show that the mechanism of somatic nuclear division in Tetrahymena, known as amitosis, provides benefits similar to sex, allowing for the long-term success of asexual lineages. We found that, when compared to mitosis, amitosis with chromosome copy number control reduces mutation load deterministically, slows the accumulation of deleterious mutations under genetic drift, and accelerates adaptation. These benefits arise because, like sex, amitosis can generate substantial genetic variation in fitness among (asexual) progeny. Our results indicate that the ability of Tetrahymena to persist in the absence of sex may depend on non-sexual genetic mechanisms conferring benefits typically provided by sex, as has been found in other asexual lineages.
Intragenic Recombination Influences Rotavirus Diversity and Evolution
Authors: Hoxie Irene , Dennehy John J.
Published: October 2019

Because of their replication mode and segmented dsRNA genome, homologous recombination is assumed to be rare in the rotaviruses. We analyzed 23,627 complete rotavirus genome sequences available in the NCBI Virus Variation database, and found 109 instances of homologous recombination, at least 11 of which prevailed across multiple sequenced isolates. In one case, recombination may have generated a novel rotavirus VP1 lineage. We also found strong evidence for intergenotypic recombination in which more than one sequence strongly supported the same event, particularly between different genotypes of segment 9, which encodes the serotype protein, VP7. The recombined regions of many putative recombinants showed amino acid substitutions differentiating them from their major and minor parents. This finding suggests that these recombination events were not overly deleterious, since presumably these recombinants proliferated long enough to acquire adaptive mutations in their recombined regions. Protein structural predictions indicated that, despite the sometimes substantial amino acid replacements resulting from recombination, the overall protein structures remained relatively unaffected. Notably, recombination junctions appear to occur non-randomly with hot spots corresponding to secondary RNA structures, a pattern seen consistently across segments. In total, we found strong evidence for recombination in nine of eleven rotavirus A segments. Only segment 7 (NSP3) and segment 11 (NSP5) did not show strong evidence of recombination. Collectively, the results of our computational analyses suggest that, contrary to the prevailing sentiment, recombination may be a significant driver of rotavirus evolution and may influence circulating strain diversity.
A plant host enables the heterologous production and combinatorial study of fungal lignin-degrading enzymes
Authors: Khlystov Nikita A. , Yoshikuni Yasuo , Deutsch Samuel , Sattely Elizabeth S.
Published: October 2019

Lignin has significant potential as an abundant and renewable source for commodity chemicals yet remains vastly underutilized. Efforts towards engineering a biochemical route to the valorization of lignin are currently limited by the lack of a suitable heterologous host for the production of lignin-degrading enzymes. Here, we show that expression of fungal genes inNicotiana benthamianaenables production of members from seven major classes of enzymes associated with lignin degradation (23 of 35 tested) in soluble form for direct use in lignin activity assays. We combinatorially characterized a subset of these enzymes in the context of model lignin dimer oxidation, revealing that fine-tuned coupling of peroxide-generators to peroxidases results in more extensive C-C bond cleavage compared to direct addition of peroxide. Comparison of peroxidase isoform activity revealed that the extent of C-C bond cleavage depends on peroxidase identity, suggesting that peroxidases are individually specialized in the context of lignin oxidation. We anticipate the use ofN. benthamianaas a platform to rapidly produce a diverse array of fungal lignin-degrading enzymes will facilitate a better understanding of their concerted role in nature and unlock their potential for lignin valorization, including within the plant host itself.
Minimally invasive classification of pediatric solid tumors using reduced representation bisulfite sequencing of cell-free DNA: a proof-of-principle study
Authors: Van Paemel Ruben , De Koker Andries , Vandeputte Charlotte , van Zogchel Lieke , Lammens Tim , Laureys Geneviève , Vandesompele Jo , Schleiermacher Gudrun , Chicard Mathieu , Van Roy Nadine , Vicha Ales , Tytgat G.A.M. , Callewaert Nico , De Preter Katleen , De Wilde Bram
Published: October 2019

In the clinical management of pediatric solid tumors, histological examination of tumor tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumor is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumor samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of pediatric tumors using cell-free reduced representation bisulfite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumor type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in pediatric oncology in a cost-effective and minimally invasive manner.

Translational relevance

Obtaining a correct diagnosis in pediatric oncology can be challenging in some tumor types, especially in renal tumors or central nervous system tumors. Furthermore, the diagnostic odyssey can result in anxiety and discomfort for these children. By applying a novel technique, reduced representation bisulfite sequencing on cell-free DNA (cf-RRBS), we show the feasibility of obtaining the histopathological diagnosis with a minimally invasive test on either plasma or cerebrospinal fluid. Furthermore, we were able to derive the copy number profile or tumor subtype from the same assay. Given that primary tumor material might be difficult to obtain, in particular in critically ill children or depending on the tumor location, and might be limited in terms of quantity or quality, our assay could become complementary to the classical tissue biopsy in difficult cases.
Multi-scale spatial genetic structure of a vector-borne plant pathogen in orchards and wild habitat
Authors: Marie-Jeanne Véronique , Bonnot François , Thébaud Gaël , Peccoud Jean , Labonne Gérard , Sauvion Nicolas
Published: October 2019

Inferring the dispersal processes of vector-borne plant pathogens is a great challenge because the plausible epidemiological scenarios often involve complex spread patterns at multiple scales. European stone fruit yellows (ESFY), a disease caused by ‘CandidatusPhytoplasma prunorum’ and disseminated via planting material and vectors belonging to the speciesCacopsylla pruni, is a major threat for stone fruit production throughout Europe. The spatial genetic structure of the pathogen was investigated at multiple scales by the application of a combination of statistical approaches to a large dataset obtained through the intensive sampling of the three ecological compartments hosting the pathogen (psyllids, wild and cultivatedPrunus) in threePrunus-growing regions in France. This work revealed new haplotypes of ‘Ca. P. prunorum’, and showed that the prevalence of the different haplotypes of this pathogen is highly uneven between all regions, and within two of them. In addition, we identified a significant clustering of similar haplotypes within a radius of at most 50 km, but not between nearby wild and cultivatedPrunus. We also provide evidence that the two species of theC. prunicomplex are unevenly distributed but can spread the pathogen, and that infected plants are transferred between production areas. Altogether, this work supports a main epidemiological scenario where ‘Ca. P. prunorum’ is endemic in, and mostly acquired from, wildPrunusby immatureC. pruni(of both species) who then migrate to “shelter plants” that epidemiologically connect sites less than 50 km apart by later providing infectious matureC. prunito their “migration basins”, which differ in their haplotypic composition. We argue that such multiscale studies would be very useful for other pathosystems.
PRC2 bridges non-adjacent nucleosomes to establish heterochromatin
Authors: Leicher Rachel , Ge Eva J. , Lin Xingcheng , Reynolds Matthew J. , Walz Thomas , Zhang Bin , Muir Tom W. , Liu Shixin
Published: October 2019

Polycomb repressive complex 2 (PRC2) maintains transcriptionally silent heterochromatin by installing and spreading repressive histone methylation marks along nucleosome arrays. Despite extensive research, the mechanism by which PRC2 engages with chromatin remains incompletely understood. Here we employ single-molecule force spectroscopy and molecular dynamics simulations to dissect the interactions of PRC2 with polynucleosome substrates. Our results reveal an unexpectedly diverse repertoire of PRC2 binding configurations on chromatin. Besides interacting with bare DNA, mononucleosomes, and neighboring nucleosome pairs, PRC2 is also found to bridge non-adjacent nucleosomes, an activity associated with chromatin compaction. Furthermore, the distribution and stability of these PRC2–chromatin interaction modes are differentially modulated by accessory PRC2 cofactors, oncogenic histone mutations, and the methylation state of chromatin. Overall, this work provides a paradigm for understanding the physical basis of epigenetic maintenance mediated by Polycomb group proteins.
Noise propagation shapes condition-dependent gene expression noise inEscherichia coli
Authors: Urchueguía Arantxa , Galbusera Luca , Bellement Gwendoline , Julou Thomas , Nimwegen Erik van
Published: October 2019

Although it is well appreciated that gene expression is inherently noisy and that transcriptional noise is encoded in a promoter’s sequence, little is known about the variation in transcriptional noise across growth conditions. Using flow cytometry we here quantify transcriptional noise inE. coligenome-wide across 8 growth conditions, and find that noise and gene regulation are intimately coupled. Apart from a growth-rate dependent lower bound on noise, we find that individual promoters show highly condition-dependent noise and that condition-dependent expression noise is shaped by noise propagation from regulators to their targets. A simple model of noise propagation identifies TFs that most contribute to both condition-specific and condition-independent noise propagation. The overall correlation structure of sequence and expression properties ofE. coligenes uncovers that genes are organized along two principal axes, with the first axis sorting genes by their mean expression and evolutionary rate of their coding regions, and the second axis sorting genes by their expression noise, the number of regulatory inputs in their promoter, and their expression plasticity.
Spans attributed to short-term memory are explained by sensitivity to long-term statistics in both musicians and individuals with dyslexia
Authors: Kimel Eva , Weiss Atalia Hai , Jakoby Hilla , Daikhin Luba , Ahissar Merav
Published: October 2019

Reduced short-term memory (STM) of individuals with dyslexia (IDDs) and enhanced STM of musicians are well documented, yet their causes are disputed. We hypothesized that their STMs reflect their sensitivities to accumulative long-term stimuli statistics. Indeed, when performing an STM task, IDDs had reduced benefit from syllable frequency, whereas musicians manifested an opposite effect, compared to controls. Interestingly, benefit from sequence-repetition did not significantly differ between groups, suggesting that it relies on different mechanisms. To test the generality of this separation across populations, we recruited a group of good-readers, whose native language contains a smaller fraction of the high-frequency syllables. Their span for these “high-frequency” syllables was small, yet their benefit from sequence-repetition was adequate. These experiments indicate that sensitivity to long-term stimuli distribution, and not to sequential repetition, is reduced in IDDs and enhanced in musicians, and this accounts for differences in their STM performance.
From ridge tops to ravines: landscape drivers of chimpanzee ranging patterns
Authors: Green Samantha J. , Boruff Bryan J. , Grueter Cyril C.
Published: October 2019

Recent improvements in tracking technologies have resulted in a growing number of fine-scale animal movement studies in a variety of fields from wildlife management to animal cognition. Most studies assume that an animal’s “optimal” foraging route is linear, ignoring the role the energy landscape can play in influencing movement efficiency. Our objective was to investigate whether landscape features that affect movement costs; topographic variation, and super and substrate, influence the movement of chimpanzees (Pan troglodytes) in a rugged, montane environment. We tested for route re-use and preferential use of human-made trails and ridge tops using 14 months of focal follow data from 14 individuals and maps of established chimpanzee trails. Chimpanzees travelled on human-made trails significantly more than expected and showed weak preference for use of ridge tops for travel. Line density analysis demonstrated route re-use in chimpanzees and uncovered a network of high-use routes across their range. To our knowledge, this is the first study to empirically demonstrate route re-use and preferential use of human-made trails for travel by chimpanzees. We discuss the energetic and cognitive benefits of trail use and the implications for chimpanzee sociality. By applying the latest GIS analytical techniques to fine-scale movement data, this study demonstrates the importance of incorporating landscape features in predictive animal movement models.