bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous MRI-EEG during a motor imagery neurofeedback task: an open access brain imaging dataset for multi-modal data integration
Authors: Lioi Giulia , Cury Claire , Perronnet Lorraine , Mano Marsel , Bannier Elise , Lécuyer Anatole , Barillot Christian
Published: December 2019

Combining EEG and fMRI allows for integration of fine spatial and accurate temporal resolution yet presents numerous challenges, noticeably if performed in real-time to implement a Neurofeedback (NF) loop. Here we describe a multimodal dataset of EEG and fMRI acquired simultaneously during a motor imagery NF task, supplemented with MRI structural data. The study involved 30 healthy volunteers undergoing five training sessions. We showed the potential and merit of simultaneous EEG-fMRI NF in previous work. Here we illustrate the type of information that can be extracted from this dataset and show its potential use. Our group is the second in the world to have integrated EEG and fMRI for NF, therefore this dataset is unique of its kind. We believe that it will be a valuable tool to

Advance and test methodologies to integrate complementary neuroimaging techniques (design and validation of methods of multi-modal data integration at various scales)

Improve the quality of Neurofeedback provided

Improve methodologies for de-noising EEG acquired under MRI

Investigate the neuromarkers of motor-imagery using multi-modal information
Neuropsychiatric mutations delineate functional brain connectivity dimensions contributing to autism and schizophrenia
Authors: Moreau Clara , Urchs Sebastian , Kuldeep Kumar , Orban Pierre , Schramm Catherine , Dumas Guillaume , Labbe Aurélie , Huguet Guillaume , Douard Elise , Quirion Pierre-Olivier , Lin Amy , Kushan Leila , Grot Stephanie , Luck David , Mendrek Adrianna , Potvin Stephane , Stip Emmanuel , Bourgeron Thomas , Evans Alan C. , Bearden Carrie E. , Bellec Pierre , Jacquemont Sebastien ,   Simons Variation in Individuals Project Consortium
Published: December 2019

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear.

We analyzed resting-state functional magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We used CNV FC-signatures to identify dimensions contributing to complex idiopathic conditions.

CNVs had large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions played a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibited worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.
Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and major groove recognition by triplex-forming oligonucleotides
Authors: Pyne Alice L. B. , Noy Agnes , Main Kavit , Velasco-Berrelleza Victor , Piperakis Michael M. , Mitchenall Lesley A. , Cugliandolo Fiorella M. , Beton Joseph G. , Stevenson Clare E.M. , Hoogenboom Bart W. , Bates Andrew D. , Maxwell Anthony , Harris Sarah A.
Published: December 2019

In the cell, DNA is arranged into highly-organised and topologically-constrained (supercoiled) structures. It remains unclear how this supercoiling affects the detailed double-helical structure of DNA, largely because of limitations in spatial resolution of the available biophysical tools. Here, we overcome these limitations, by a combination of atomic force microscopy (AFM) and atomistic molecular dynamics (MD) simulations, to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution. We observe that negative superhelical stress induces local variation in the canonical B-form DNA structure by introducing kinks and defects that affect global minicircle structure and flexibility. We probe how these local and global conformational changes affect DNA interactions through the binding of triplex-forming oligonucleotides to DNA minicircles. We show that the energetics of triplex formation is governed by a delicate balance between electrostatics and bonding interactions. Our results provide mechanistic insight into how DNA supercoiling can affect molecular recognition, that may have broader implications for DNA interactions with other molecular species.
Disorder and interfaces in proteins are two sides of the same coin
Authors: Seoane Beatriz , Carbone Alessandra
Published: December 2019

The importance of unstructured biology has quickly grown during the last decades accompanying the explosion of the number of experimentally resolved structures. The idea that structural disorder might be a novel mechanism of protein interaction is widespread in the literature, although the number of statistically significant structural studies supporting this idea is surprisingly low. In this work, through a large-scale-analysis of all the crystallographic structures of the Protein Data Bank averaged over clusters of homologous sequences, we show clear evidences that both the (experimentally verified) interaction interfaces and the disordered regions are involving roughly the same amino-acids of the protein. And beyond, disordered regions appear to carry information about the location of alternative interfaces when the protein lies within complexes, thus playing an important role in determining the order of assembly of protein complexes.
Linear alkylbenzenes (LABs) as sewage pollution indicators in the aquatic ecosystem of Peninsular Malaysia
Authors: Alkhadher Sadeq. A. A. , Kadir Aeslina Abdul , Zakaria Mohamad Pauzi
Published: December 2019

Linear alkylbenzenes (LABs) as sewerage indicators were investigated in the sediments of the West and South Peninsular Malaysia. Surface sediment samples were analyzed using gas chromatography–mass spectrometry. Results showed that LAB concentration in the samples of Port Dickson and the Kim Kim River varied from 111.6 to 255.8 and from 88.2 to 119.0 ng·g−1 dry weight, respectively. The ratios of internal isomer, in which the benzene ring was close to the center of the linear alkyl chain, to external isomer, in which the benzene ring was near the end of the linear alkyl chain (I/E ratios), of LABs in Port Dickson coast sediments ranged from 2.6 to 4.1. By contrast, the ratios for sediment from the Kim Kim River varied from 1.7 to 1.9. I/E, long-chained LABs over short-chained LABs (L/S), and C13/C12 ratios indicated that the aquatic environment received primary and secondary sewage effluents. These findings emphasized the necessity of continued water treatment system development in Malaysia.
Decay and damage of therapeutic phage OMKO1 by environmental stressors
Authors: Blazanin Michael , Lam Wai Tin , Vasen Emma , Chan Benjamin K. , Turner Paul E.
Published: December 2019

Antibiotic resistant bacterial pathogens are increasingly prevalent, driving the need for alternative approaches to chemical antibiotics when treating infections. One such approach is bacteriophage therapy: the use of bacteria-specific viruses that lyse (kill) their host cells. Just as the effect of environmental conditions (e.g. elevated temperature) on antibiotic efficacy is well-studied, the effect of environmental stressors on the potency of phage therapy candidates demands examination. Therapeutic phage OMKO1 infects and kills the opportunistic human pathogen Pseudomonas aeruginosa. Here, we used phage OMKO1 as a model to test how different environments affect the decay rate of a therapeutic virus, and whether exposure to an environmental stressor can damage surviving viral particles. We assessed the effects of elevated temperatures, saline concentrations, and urea concentrations. We observed that OMKO1 particles were highly tolerant to different saline concentrations, but decayed more rapidly at elevated temperatures and under high concentrations of urea. Additionally, we found that exposure to elevated temperature reduced the ability of surviving phage particles to suppress the growth of P. aeruginosa, suggesting a temperature-induced damage. Our findings demonstrate that OMKO1 is highly tolerant to a range of conditions that could be experienced inside and outside the human body, while also showing the need for careful characterization of therapeutic phages to ensure that environmental exposure does not compromise their expected potency, dosing, and pharmacokinetics.
Chemogenetic actuator drugs impair prefrontal cortex-dependent working memory in rhesus monkeys
Authors: Upright Nicholas A. , Baxter Mark G.
Published: December 2019

The most common chemogenetic neuromodulatory system, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is no longer sensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug. We investigated working memory performance after injections of three DREADD agonists, clozapine, olanzapine, and deschloroclozapine, in male rhesus monkeys tested in a spatial delayed response task. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from mean performance after vehicle in any of the four subjects. Administration of 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after administration of 0.1 mg/kg olanzapine and two monkeys were impaired after the 0.3 mg/kg dose of deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs to confirm that effects following DREADD receptor transduction are not due to the actuator drug itself, as well as validating the behavioral pharmacology of DREADD actuator drugs in the specific tasks under study.

Significance Statement

Chemogenetic technologies, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), allow for precise and remote manipulation of neuronal circuits. In the present study, we tested monkeys in a spatial delayed response task after injections of three actuator drugs – clozapine, olanzapine, and deschloroclozapine. We found that monkeys showed significant working memory impairments after 0.2 mg/kg clozapine, 0.1 mg/kg olanzapine, and 0.3 mg/kg deschloroclozapine compared to vehicle performance. In monkeys that showed impairments, these deficits were particularly apparent at longer delay periods. It is imperative to validate the drugs and dosages in the particular behavioral test to ensure any behavior after DREADD transduction can be attributed to activation of the receptors and not administration of the actuator drug itself.
NK cells negatively regulate CD8 T cells to promote immune exhaustion and chronicToxoplasma gondiiinfection
Authors: Ivanova Daria L. , Krempels Ryan , Denton Stephen L. , Fettel Kevin D. , Saltz Giandor M. , Rach David , Fatima Rida , Mundhenke Tiffany , Materi Joshua , Dunay Ildiko R. , Gigley Jason P.
Published: December 2019

NK cells regulate CD4+ and CD8+ T cells in acute viral infection, vaccination and the tumor microenvironment. NK cells also become exhausted in chronic activation settings. The mechanisms causing these ILC responses and their impact on adaptive immunity are unclear. CD8+ T cell exhaustion develops during chronicToxoplasma gondii(T. gondii) infection resulting in parasite reactivation and death. How chronicT. gondiiinfection impacts the NK cell compartment is not known. We demonstrate that NK cells do not exhibit hallmarks of exhaustion. Their numbers are stable and they do not express high PD1 or LAG3. NK cell depletion with anti-NK1.1 is therapeutic and rescues chronicT. gondiiinfected mice from CD8+ T cell exhaustion dependent death, increases survival after lethal secondary challenge and reduces parasite reactivation. Anti-NK1.1 treatment increased polyfunctional CD8+ T cell responses in spleen and brain and reduced CD8+ T cell apoptosis. ChronicT. gondiiinfection promotes the development of a modified NK cell compartment, which does not exhibit normal NK cell behavior. This splenic CD49a-CD49b+NKp46+ NK cell population develops during the early chronic phase of infection and increases through the late chronic phase of infection. They are Ly49 and TRAIL negative and are enriched for expression of CD94/NKG2A and KLRG1. They do not produce IFNγ, are IL-10 negative, do not increase PDL1 expression, but do increase CD107a on their surface. They are also absent from brain. Based on the NK cell receptor phenotype we observed NKp46 and CD94-NKG2A cognate ligands were measured. Activating NKp46 (NCR1-ligand) ligand increased and NKG2A ligand Qa-1b expression was reduced. Blockade of NKp46 also rescued the chronically infected mice from death. Immunization with a single dose non-persistent 100% protectiveT. gondiivaccination did not induce this cell population in the spleen, suggesting persistent infection is essential for their development. We hypothesize chronicT. gondiiinfection induces an NKp46 dependent modified NK cell population that reduces functional CD8+ T cells to promote persistent parasite infection in the brain. NK cell targeted therapies could enhance immunity in people with chronic infections, chronic inflammation and cancer.
Flanker task-elicited Event Related Potential sources reflect human recombinant Erythropoietin differential effects on Parkinson’s patients
Authors: Vega Maria L Bringas , Liu Shengnan , Zhang Min , Ibañez Ivonne Pedroso , Chacon Lilia M. Morales , Garcia Lidice Galan , Bocourt Vanessa Perez , Jahanshahi Marjan , Valdes-Sosa Pedro A
Published: December 2019

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson’ s Disease patients.

The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low-resolution tomography (LORETA) inverse solution was employed to localize the neural generators.

Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs.

From our results rHuEPO, seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus evoked by incongruent stimuli differentiated PD and HCs.
3dSpAn: An interactive software for 3D segmentation and analysis of dendritic spines
Authors: Das Nirmal , Baczynska Ewa , Bijata Monika , Ruszczycki Blazej , Zeug Andre , Plewczynski Dariusz , Saha Punam Kumar , Ponimaskin Evgeni , Wlodarczyk Jakub , Basu Subhadip
Published: December 2019

Three dimensional segmentation and analysis of dendritic spines involve two major challenges: 1) how to segment individual spines from the dendrites and 2) how to quantitatively assess the morphology of individual spines. We developed a software named 3dSpAn to address these two issues by implementing our previously published 3D multiscale opening algorithm in shared intensity space and using effective morphological features for individual dendritic spine plasticity analysis. 3dSpAn consists of four modules: Preprocessing and ROI selection, Intensity thresholding and seed selection, Multiscale segmentation and Quantitative morphological feature extraction. We show the results of segmentation and morphological analysis for different observation methods, includingin vitroandex vivoimaging with confocal microscopy, andin vivosamples, using high-resolution two-photon microscopy. The software is freely available, the source code, windows installer, the software manual and video tutorial can be obtained from:https://sites.google.com/view/3dSpAn/.
RePAIR: a power solution to animal experimentation
Authors: Bonapersona V. , Hoijtink H. ,   RELACS, Sarabdjitsingh R.A. , Joëls M.
Published: December 2019

Low statistical power challenges the reliability of animal research; yet, increasing sample sizes to the required level raises important ethical and practical issues. We present an alternative solution, RePAIR, which capitalizes on the observation that control groups in general are expected to be similar to each other. As shown in a simulation study, including information of previous control experiments in the statistical analysis using RePAIR reduced the required sample size by 49% or increased power up to 100%. We validated the potential of RePAIR in a unique dataset based on 7 independent experiments across the world, studying cognitive effects of early life adversity in mice. RePAIR comes with an open-source web-based tool and can be widely used to largely improve quality of animal experimentation.

One Sentence Summary

Prior studies’ information can reduce use of animals or increase statistical power, improving animal research reliability
Tracking selective rehearsal and active inhibition of memory traces in directed forgetting
Authors: Fellner Marie-Christin , Waldhauser Gerd T. , Axmacher Nikolai
Published: December 2019

Selectively remembering or forgetting newly encountered information is essential for goal-directed behavior. It is still an open question, however, whether intentional forgetting is an active process based on the inhibition of unwanted memory traces or whether it occurs passively through reduced recruitment of selective rehearsal [1,2]. Here we show that intentional control of memory encoding relies on both, enhanced active inhibition and decreased selective rehearsal, and that these two processes can be separated in time and space. We applied representational similarity analysis (RSA [3]) and timefrequency analysis to EEG data during an item-method directed forgetting experiment [4]. We identified neural signatures of both the intentional suppression and the voluntary upregulation of item-specific representations. Successful active forgetting was associated with a downregulation of item-specific representations in an early time window, 500ms after the instruction. This process was initiated by an increase in oscillatory alpha (8-13 Hz) power, a well-established signature of neural inhibition [5,6], in occipital brain areas. During a later time window, 1500ms after the cue, intentional forgetting was associated with reduced employment of active rehearsal processes, as reflected by an attenuated upregulation of item-specific representations as compared to intentionally encoded items. Our data show that active inhibition and selective rehearsal are two separate mechanisms whose consecutive employment allows for a voluntary control of memory formation.
Transcription factor motifs associated with anterior insula gene-expression underlying mood disorder phenotypes
Authors: Arasappan Dhivya , Eickhoff Simon B. , Nemeroff Charles B , Hofmann Hans A. , Jabbi Mbemba
Published: December 2019

Background

Mood disorders represent a major cause of morbidity and mortality worldwide but the brain-related molecular pathophysiology in mood disorders remains largely undefined.

Methods

Because the anterior insula is reduced in volume in patients with mood disorders, RNA was extracted from postmortem mood disorder samples and compared with unaffected control samples for RNA-sequencing identification of differentially expressed genes (DEGs) ina) bipolar disorder (BD; n=37) versus (vs.) controls (n=33), andb) major depressive disorder (MDD n=30) vs controls, andc) low vs. high Axis-I comorbidity (a measure of cumulative psychiatric disease burden). Given the regulatory role of transcription factors (TFs) in gene expression via specific-DNA-binding domains (motifs), we used JASPAR TF binding database to identify TF-motifs.

Results

We found that DEGs in BD vs. controls, MDD vs. controls, and high vs. low Axis-I comorbidity were associated with TF-motifs that are known to regulate expression of toll-like receptor genes, cellular homeostatic-control genes, and genes involved in embryonic, cellular/organ and brain development.

Discussion

Robust imaging-guided transcriptomics(i.e., using meta-analytic imaging results to guide independent post-mortem dissection for RNA-sequencing) was applied by targeting the gray matter volume reduction in the anterior insula in mood disorders, to guide independent postmortem identification of TF motifs regulating DEG. TF motifs were identified for immune, cellular, embryonic and neurodevelopmental processes.

Conclusion

Our findings of TF-motifs that regulate the expression of immune, cellular homeostatic-control, and developmental genes provides novel information about the hierarchical relationship between gene regulatory networks, the TFs that control them, and proximate underlying neuroanatomical phenotypes in mood disorders.
From Modulated Noise to Natural Speech: the Effect of Stimulus Parameters on the Frequency Following Response
Authors: Van Canneyt Jana , Wouters Jan , Francart Tom
Published: December 2019

Frequency following responses (FFRs) can be evoked by a wide range of auditory stimuli, but for many stimulus parameters the effect on FFR strength is not fully understood. This complicates the comparison of earlier studies and the design of new studies. Furthermore, the most optimal stimulus parameters are unknown. To help resolve this issue, we investigated the effects of four important stimulus parameters and their interactions on the FFR. FFRs were measured in 16 normal hearing subjects evoked by stimuli with four levels of stimulus complexity (amplitude modulated noise, artificial vowels, natural vowels and nonsense words), three frequencies (around 105 Hz, 185 Hz and 245 Hz), three frequency contours (upward sweeping, downward sweeping and flat) and three vowels (Flemish /a:/, /u:/, and /i:/). We found that FFRs evoked by artificial vowels were on average 4 to 6 dB SNR larger than responses evoked by the other stimulus complexities, probably because of (unnaturally) strong higher harmonics. Moreover, response amplitude decreased with stimulus frequency but response SNR did not. Thirdly, frequency variation within the stimulus did not impact FFR strength, but only when rate of change remained low (e.g. not the case for sweeping natural vowels). Finally, the vowel /i:/ appeared to evoke larger response amplitudes compared to /a:/ and /u:/, but analysis power was too small to confirm this statistically. Differences in response strength between evoking vowels have been suggested to stem from destructive interference between response components. We show how a model of the auditory periphery can simulate these interference patterns and predict response strength. Altogether, the results of this study can guide stimulus choice for future FFR research and practical applications.
Dopamine differentially modulates the size of projection neuron ensembles in the intact and dopamine-depleted striatum
Authors: Maltese Marta , March Jeffrey R. , Bashaw Alexander G. , Tritsch Nicolas X.
Published: December 2019

Dopamine (DA) is a critical modulator of brain circuits that control voluntary movements, but our understanding of its influence on the activity of target neurons in vivo remains limited. Here, we use two-photon Ca2+ imaging to monitor the activity of direct and indirect-pathway spiny projection neurons (SPNs) simultaneously in the striatum of behaving mice during acute and prolonged manipulations of DA signaling. We find that increasing and decreasing DA biases striatal activity towards the direct and indirect pathways, respectively, by changing the overall number of SPNs recruited during behavior in a manner not predicted by existing models of DA function. This modulation is drastically altered in a model of Parkinson’s disease. Our results reveal a previously unappreciated population-level influence of DA on striatal output and provide novel insights into the pathophysiology of Parkinson’s disease.
A Distinct Contractile Injection System Found in a Majority of Adult Human Microbiomes
Authors: Rojas Maria I. , Cavalcanti Giselle S. , McNair Katelyn , Benler Sean , Alker Amanda T. , Cobián-Güemes Ana G. , Giluso Melissa , Levi Kyle , Rohwer Forest , Beyhan Sinem , Edwards Robert A. , Shikuma Nicholas J.
Published: December 2019

An imbalance of normal bacterial groups such as Bacteroidales within the human gut is correlated with diseases like obesity. A current grand challenge in the microbiome field is to identify factors produced by normal microbiome bacteria that cause these observed health and disease correlations. While identifying factors like a bacterial injection system could provide a missing explanation for why Bacteroidales correlates with host health, no such factor has been identified to date. The lack of knowledge about these factors is a significant barrier to improving therapies like fecal transplants that promote a healthy microbiome. Here we show that a previously ill-defined Contractile Injection System is carried in the gut microbiome of 99% of individuals from the United States and Europe. This type of Contractile Injection System, we name here Bacteroidales Injection System (BIS), is related to the contractile tails of bacteriophage (viruses of bacteria) and have been described to mediate interactions between bacteria and diverse eukaryotes like amoeba, insects and tubeworms. Our findings that BIS are ubiquitous within adult human microbiomes suggest that they shape host health by mediating interactions between Bacteroidales bacteria and the human host or its microbiome.
Bacteria contribute to plant secondary compound degradation in a generalist herbivore system
Authors: Francoeur Charlotte B. , Khadempour Lily , Moreira-Soto Rolando D. , Gotting Kirsten , Book Adam J. , Pinto-Tomás Adrián A. , Keefover-Ring Ken , Currie Cameron R.
Published: December 2019

Herbivores must overcome a variety of plant defenses, including coping with plant secondary compounds (PSCs). To help detoxify these defensive chemicals, several insect herbivores are known to harbor gut microbiota with the metabolic capacity to degrade PSCs. Leaf-cutter ants are generalist herbivores, obtaining sustenance from specialized fungus gardens that act as external digestive systems, degrading the diverse collection of plants foraged by the ants. There isin vitroevidence that certain PSCs harmLeucoagaricus gongylophorus, the fungal cultivar of leaf-cutter ants, suggesting a role for the Proteobacteria-dominant bacterial community present within fungus gardens. Here, we investigate the ability of symbiotic bacteria present within fungus gardens of leaf-cutter ants to degrade PSCs. We cultured fungus garden bacteria, sequenced the genomes of 42 isolates, and identified genes involved in PSC degradation, including genes encoding cytochrome p450s and genes in geraniol, cumate, cinnamate, and α-pinene/limonene degradation pathways. Using metatranscriptomic analysis, we show that some of these degradation genes are expressedin situ. Most of the bacterial isolates grew unhindered in the presence of PSCs and, using GC-MS, we determined that isolates from the generaBacillus, Burkholderia, Enterobacter, Klebsiella,andPseudomonasdegrade α-pinene, β-caryophyllene, or linalool. Using a headspace sampler, we show that sub-colonies of fungus gardens reduced α-pinene and linalool over a 36-hour period, whileL. gongylophorusstrains alone only reduced linalool. Overall, our results reveal that the bacterial community in fungus gardens play a pivotal role in alleviating the effect of PSCs on the leaf-cutter ant system.

Importance

Leaf-cutter ants are dominant neotropical herbivores capable of deriving energy from a wide range of plant substrates. The success of leaf-cutter ants is largely due to their external gut composed of key microbial symbionts, specifically, the fungal mutualistL. gongylophorusand a consistent bacterial community. Both symbionts are known to have critical roles in extracting energy from plant material, yet comparatively little is known about their role in the detoxification of plant secondary compounds. Here, we assess if the bacterial community associated with leaf-cutter ant fungus gardens can degrade harmful plant chemicals. We identify plant secondary compound detoxification in leaf-cutter ant gardens as a process that depends on the degradative potential of both the bacterial community andL. gongylophorus. Our findings suggest the fungus garden and its associated microbial community influences the generalist foraging abilities of the ants, underscoring the importance of microbial symbionts in plant substrate suitability for herbivores.
The demyelinating agent cuprizone induces a male-specific reduction in binge eating in the binge-prone C57BL/6NJ strain
Authors: Babbs Richard K. , Beierle Jacob A. , Kelliher Julia C. , Medeiros Rose , Anandakumar Jeya , Shah Anyaa , Yao Emily J. , Chen Melanie M. , Bryant Camron D.
Published: December 2019

Binge eating (BE) is a heritable symptom of eating disorders with an unknown genetic etiology. Rodent models for BE of palatable food permit the study of genetic and biological mechanisms. We previously used genetic mapping and transcriptome analysis to map a coding mutation inCyfip2associated with increased BE in the BE-prone C57BL/6NJ substrain compared to the BE-resistant C57BL/6J substrain. The increase in BE in C57BL/6NJ mice was associated with a decrease in transcription of genes enriched for myelination in the striatum. Here, we tested the hypothesis that decreasing myelin levels with the demyelinating agent cuprizone would enhance BE. Mice were treated with a 0.3% cuprizone home cage diet for two weeks. Following a three-week recovery period, mice were trained for BE in an intermittent, limited access procedure. Cuprizone induced similar weight loss in both substrains and sexes that recovered within 48 h after removal of the cuprizone diet. Surprisingly, cuprizone reduced BE in male but not female C57BL/6NJ mice while having no effect in C57BL/6J mice. Cuprizone also reduced myelin basic protein (MBP) at seven weeks post-cuprizone removal while having no effect on myelin-associated glycoprotein (MAG) at this time point. C57BL/6N mice also showed less MBP than C57BL/6J mice. There were no statistical interactions of Treatment with Sex on MBP levels, indicating that differences in MBP are unlikely to account for sex differences in BE. To summarize, cuprizone induced an unexpected, male-specific reduction in BE which could indicate sex-specific biological mechanisms that depend on genetic background.
An updated antennal lobe atlas for the yellow fever mosquitoAedes aegypti
Authors: Shankar Shruti , McMeniman Conor J.
Published: December 2019

The yellow fever mosquitoAedes aegyptiis a prolific vector of arboviral and filarial diseases that largely relies on its sense of smell to find humans. To facilitate in-depth analysis of the neural circuitry underlyingAe. aegyptiolfactory-driven behaviors, we generated an updatedin vitroatlas for the antennal lobe olfactory brain region of this disease vector using two independent neuronal staining methods. We performed morphological reconstructions with replicate fixed, dissected and stained brain samples from adult male and femaleAe. aegyptiof the LVPib12 genome reference strain and determined that the antennal lobe in both sexes is comprised of approximately 80 discrete glomeruli. Guided by landmark features in the antennal lobe, we found 63 of these glomeruli are stereotypically located in spatially invariant positions within thesein vitropreparations. A posteriorly positioned, mediodorsal glomerulus denoted MD1 was identified as the largest spatially invariant glomerulus in the antennal lobe. Spatial organization of glomeruli in a recently field-derived strain ofAe. aegyptifrom Puerto Rico was conserved, despite differences in antennal lobe shape relative to the inbred LVPib12 strain. This modelin vitroatlas will serve as a useful community guide and resource to improve antennal lobe annotation and anatomically map projection patterns of neurons expressing target genes in this olfactory center. It will also facilitate the development of chemotopic maps of odor representation in the mosquito antennal lobe to decode the molecular and cellular basis ofAe. aegyptiattraction to human scent and other chemosensory cues.

Author Summary

The olfactory system of the yellow fever mosquitoAedes aegyptiis highly tuned for the detection of human odorants, as well as other chemical cues influencing host and food-search behavior, egg-laying and mating. To provide insights into the neuroanatomical organization of the olfactory system of this globally important disease vector, we have generated an updatedin vitroatlas for the primary smell processing center of theAe. aegyptibrain, called the antennal lobe. These new guide maps facilitate systematic interrogation of antennal lobe morphology and naming of associated substructures in dissected brain samples of this species labeled with two common neural staining methods. We report that landmark features of theAe. aegyptiantennal lobe morphology and spatial organization appear conserved between mosquito sexes and across geographically divergent strains of this mosquito species. An improved understanding ofAe. aegyptiantennal lobe neuroanatomy and how attractive or repellent odorant stimuli are encoded in this brain center has the potential to rapidly accelerate reverse engineering of synthetic chemical blends that effectively lure, confuse or repel this major disease vector.
Serial assessment of iron in the motor cortex in limb-onset Amyotrophic Lateral Sclerosis using Quantitative Susceptibility Mapping
Authors: Bhattarai Anjan , Chen Zhaolin , Ward Phillip G. D. , Talman Paul , Mathers Susan , Phan Thanh G , Chapman Caron , Howe James , Lee Sarah , Lie Yennie , Egan Gary F , Chua Phyllis
Published: December 2019

Objective

Dysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with Amyotrophic Lateral Sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based Quantitative Susceptibility Mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a six-month period.

Methods

Iron concentration was investigated using magnetic resonance based -QSM in the primary motor cortex and the pre-motor area in thirteen limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and eleven age and sex-matched healthy controls. Nine ALS patients underwent follow-up scans at six months.

Results

Significantly increased QSM was observed in the left posterior primary motor area (p = 0.02, Cohen’s d = 0.9) and right anterior primary motor area (p = 0.02, Cohen’s d = 0.92) in all individuals with limb-onset ALS compared to healthy controls. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to healthy controls. No significant change in QSM was observed at the six-month follow-up scans in the ALS patients.

Conclusions

The findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a radiological indicator in disease diagnosis, and in clinical trials in limb-onset ALS and its subtypes.

Highlights

Serial measurement of QSM in the motor cortex in limb-onset ALS was performed

QSM changes in the motor cortex in ALS sub-groups were investigated

Higher QSM was observed in the motor cortex in Lumbar ALS relative to controls

QSM is sensitive to iron dysregulation in the motor cortex in limb-onset ALS
Neurobehavioral Correlates of How Time-on-task and Sleep Deprivation Modulate Deployment of Cognitive Effort
Authors: Massar Stijn A.A. , Lim Julian , Sasmita Karen , Ragunath Bindiya L. , Chee Michael W.L.
Published: December 2019

Sustaining attention is highly demanding and can falter if there is a shift in willingness to exert effort. Motivated attentional performance and effort preference were tracked in relation to increasing time-on-task (Experiment 1) and sleep deprivation (Experiment 2). Performance decrement with time-on-task was attenuated with reward, while preference to deploy effort decreased with longer task duration. Sleep deprivation, accentuated performance decline with time-on-task, and was accompanied by greater effort-discounting. Motivated attention performance was associated with higher fronto-parietal activation, in both normal and sleep deprived conditions. However, after sleep deprivation modulation of activation by reward was reduced in the anterior cingulate cortex (ACC) and left anterior insula (aIns). Together, these results depict how motivational decline affects performance when one gets tired after sustained task performance and/or sleep deprivation.
Relationships between aboveground plant traits and carbon cycling in tundra plant communities
Authors: Happonen Konsta , Virkkala Anna-Maria , Kemppinen Julia , Niittynen Pekka , Luoto Miska
Published: December 2019

The functional composition and diversity of plant communities are globally applicable predictors of ecosystem functioning. Yet, it is unclear how traits influence carbon cycling. This is an important question in the tundra where vegetation shifts are occurring across the entire biome, and where soil organic carbon stocks are large and vulnerable to environmental change.

To study how traits affect carbon cycling in the tundra, we built a model that explained carbon cycling (above-ground and soil organic carbon stocks, and photosynthetic and respiratory fluxes) with abiotic conditions (air temperature and soil moisture), plant community functional composition (average plant height, leaf dry matter content (LDMC) and specific leaf area (SLA)), and functional diversity (weighted standard deviations of the traits). Data was collected from an observational study setting from northern Finland.

The explanatory power of the models was relatively high, but a large part of variation in soil organic carbon stocks remained unexplained. Plant height was the strongest predictor of all carbon cycling variables except soil carbon stocks. Communities of larger plants were associated with larger CO2fluxes and above-ground carbon stocks. Communities with fast leaf economics (i.e. high SLA and low LDMC) had higher photosynthesis, ecosystem respiration, and soil organic carbon stocks.

Within-community variability in plant height, SLA, and LDMC affected ecosystem functions differently. SLA and LDMC diversity increased CO2fluxes and soil organic carbon stocks, while height diversity increased the above-ground carbon stock. The contributions of functional diversity metrics to ecosystem functioning were about as important as those of average SLA and LDMC traits.

Synthesis: Plant height, SLA, and LDMC have clear effects on tundra carbon cycling. The importance of functional diversity highlights a potentially important mechanism controlling the vast tundra carbon pools that should be better recognized. More research on root traits and decomposer communities is needed to understand the below-ground mechanisms regulating carbon cycling in the tundra.
Turbulent-like dynamics in the human brain
Authors: Deco Gustavo , Kringelbach Morten L.
Published: December 2019

Turbulence facilitates fast energy/information transfer across scales in physical systems. These qualities are important for brain function, but it is currently unknown if the dynamic intrinsic backbone of brain also exhibits turbulence. Using large-scale neuroimaging empirical data from 1003 healthy participants, we demonstrate Kuramoto’s amplitude turbulence in human brain dynamics. Furthermore, we build a whole-brain model with coupled oscillators to demonstrate that the best fit to the data corresponds to a region of maximally developed amplitude turbulence, which also corresponds to maximal sensitivity to the processing of external stimulations (information capability). The model shows the economy of anatomy by following the Exponential Distance Rule of anatomical connections as a cost-of-wiring principle. This establishes a firm link between turbulence and optimal brain function. Overall, our results reveal a way of analysing and modelling whole-brain dynamics that suggests turbulence as the dynamic intrinsic backbone facilitating large scale network communication.
The CX3CL1 oligomerization is required for efficient CX3CR1-specific cell adherence
Authors: Ostuni Mariano A. , Hermand Patricia , Saindoy Emeline , Guillou Noëlline , Guellec Julie , Coens Audrey , Hattab Claude , Desuzinges-Mandon Elodie , Jawhari Anass , Iatmanen-Harbi Soria , Lequin Olivier , Fuchs Patrick , Lacapere Jean-Jacques , Combadière Christophe , Pincet Frédéric , Deterre Philippe
Published: December 2019

During inflammatory response, blood leukocytes adhere to the endothelium. This process involves numerous adhesion molecules, including a transmembrane chemokine, CX3CL1. We previously found that CX3CL1 clusters in oligomers. How this cluster assembles and whether it has a functional role remain unknown. Using various biochemical and biophysical approaches, we show that CX3CL1 clusters are homo-oligomers with 3 to 7 CX3CL1 molecules. We demonstrate that the transmembrane domain peptide self-associates at a similar level in both cellular and acellular lipid environments while its random counterpart (a scrambled peptide) does not. Hence, oligomerization is mainly driven by the transmembrane domain intrinsic properties. Molecular modeling suggests that transmembrane peptide oligomers are mostly made of monomers linearly assembled side by side. Using a new adherence assay, we demonstrate that, functionally, oligomerization is mandatory for the adhesive potency of CX3CL1. Our results indicate that CX3CL1-dependent cellular adherence in key immune processes can be controlled by disrupting clusters using heterotopic peptides, which, in turn, alter the adhesive function of the membrane CX3CL1 without affecting the function of the CX3CL1 soluble form.
Novel Analgesic Agents Obtained by Molecular Hybridization of Orthosteric and Allosteric Ligands
Authors: Matera Carlo , Flammini Lisa , Riefolo Fabio , Domenichini Giuseppe , De Amici Marco , Barocelli Elisabetta , Dallanoce Clelia , Bertoni Simona
Published: December 2019

Despite the high incidence of acute and chronic pain in the general population, the efficacy of currently available medications is unsatisfactory. Insufficient management of pain has a profound impact on the quality of life and can have serious physical, psychological, social, and economic consequences. This unmet need reflects a failure to develop novel classes of analgesic drugs with superior clinical properties and lower risk of abuse. Nevertheless, recent advances in our understanding of the neurobiology of pain are offering new opportunities for developing different therapeutic approaches. Among those, the activation of M2 muscarinic acetylcholine receptors, which play a key role in the cholinergic regulation of the nociceptive transmission, constitutes one of the most promising strategies. We have recently developed a small library of novel pharmacological agents by merging the structures of known orthosteric and allosteric muscarinic ligands through their molecular hybridization, an emerging approach in medicinal chemistry based on the combination of pharmacophoric moieties of different bioactive substances to produce a new compound with improved pharmacological properties. Herein we report the functional characterization of the new ligands in vitro and the assessment of their efficacy as analgesic agents and tolerability in mice. This work provides new insights for the development and optimization of novel muscarinic hybrid compounds for the management of pain.
Long-read only assembly of Drechmeria coniospora genomes reveals widespread chromosome plasticity and illustrates the limitations of current nanopore methods
Authors: Courtine Damien , Provaznik Jan , Reboul Jerome , Blanc Guillaume , Benes Vladimir , Ewbank Jonathan J.
Published: December 2019

Long read sequencing is increasingly being used to determine eukaryotic genomes. We used nanopore technology to generate chromosome-level assemblies for 3 different strains of Drechmeria coniospora, a nematophagous fungus used extensively in the study of innate immunity in Caenorhabditis elegans. One natural geographical isolate demonstrated high stability over decades, whereas a second isolate, not only had a profoundly altered genome structure, but exhibited extensive instability. We conducted an in-depth analysis of sequence errors within the 3 genomes and established that even with state-of-the-art tools, nanopore methods alone are insufficient to generate eukaryotic genome sequences of sufficient accuracy to merit inclusion in public databases.
LandScape: a web application for interactive genomic summary visualization
Authors: Jia Wenlong , Li Hechen , Li Shiying , Li Shuaicheng
Published: December 2019

Visualizing integrated-level data from genomic research remains a challenge, as it requires sufficient coding skills and experience. Here, we present LandScapeoviz, a web-based application for interactive and real-time visualization of summarized genetic information. LandScape utilizes a well-designed file format that is capable of handling various data types, and offers a series of built-in functions to customize the appearance, explore results, and export high-quality diagrams that are available for publication.

Availability and implementation

LandScape is deployed at bio.oviz.org/demo-project/analyses/landscape for online use. Documentation and demo data are freely available on this website and GitHub (github.com/Nobel-Justin/Oviz-Bio-demo).

Contact

shuaicli@cityu.edu.hk