bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractFrequency 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

ABSTRACTDopamine (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

ABSTRACTAn 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

AbstractHerbivores 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.ImportanceLeaf-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

ABSTRACTBinge 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

AbstractThe 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 SummaryThe 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

ABSTRACTObjectiveDysregulation 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.MethodsIron 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.ResultsSignificantly 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.ConclusionsThe 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.HighlightsSerial measurement of QSM in the motor cortex in limb-onset ALS was performedQSM changes in the motor cortex in ALS sub-groups were investigatedHigher QSM was observed in the motor cortex in Lumbar ALS relative to controlsQSM 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

AbstractSustaining 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

AbstractThe 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

SummaryTurbulence 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

AbstractDuring 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

AbstractDespite 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.