bluuebunny/crossref_metadata_2025 huggingface dataset:
Value-related neuronal responses in the human amygdala during observational learning
Authors: Aquino Tomas G. , Minxha Juri , Dunne Simon , Ross Ian B. , Mamelak Adam N. , Rutishauser Ueli , O’Doherty John P.
Published: December 2019

The amygdala plays an important role in many aspects of social-cognition and reward-learning. Here we aimed to determine whether human amygdala neurons are involved in the computations necessary to implement learning through observation. We performed single-neuron recordings from the amygdalae of human neurosurgical patients (male and female) while they learned about the value of stimuli through observing the outcomes experienced by another agent interacting with those stimuli. We used a detailed computational modeling approach to describe patients’ behavior in the task. Then, using both population-level decoding and single neuron analyses we found evidence to implicate amygdala neurons in two key computations relevant for observational-learning: tracking the expected future reward associated with a given stimulus, and in tracking outcome values received by oneself or other agents. Encoding and decoding analyses suggested observational value coding in amygdala neurons occurred in a different subset of neurons than experiential value coding. Collectively, these findings support a key role for the human amygdala in the computations underlying the capacity for learning through observation.

Significance statement

Single neuron studies of the human brain provide a unique window into the computational mechanisms of cognition. In this study, epilepsy patients implanted intracranially with depth microelectrodes performed an observational learning task. We measured activity bilaterally in the amygdala and found a representation for observational rewards as well as observational expected reward values. Additionally, the representation of self-experienced and observational values was performed by distinct subsets of amygdala neurons. This study thus provides a rare glimpse into the role of human amygdala neurons in social cognition.
DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis
Authors: Nassar Zeyad D. , Mah Chui Yan , Dehairs Jonas , Burvenich Ingrid J.G. , Irani Swati , Centenera Margaret M. , Shrestha Raj K. , Moldovan Max , Don Anthony S. , Scott Andrew M. , Horvath Lisa G. , Lynn David J. , Selth Luke A. , Hoy Andrew J. , Swinnen Johannes V. , Butler Lisa M.
Published: December 2019

Fatty acid β-oxidation (FAO) is the main bioenergetic pathway in prostate cancer (PCa) and a promising novel therapeutic vulnerability. Here we demonstrate therapeutic efficacy of targeting FAO in clinical prostate tumors cultured ex vivo, and identify DECR1, which encodes the rate-limiting enzyme for oxidation of polyunsaturated fatty acids (PUFAs), as robustly overexpressed in PCa tissues and associated with shorter relapse-free survival. DECR1 is a negatively-regulated androgen receptor (AR) target gene and, therefore, may promote PCa cell survival and resistance to AR targeting therapeutics. DECR1 knockdown in PCa cells selectively inhibited β-oxidation of PUFAs, inhibited proliferation and migration of PCa cells, including treatment resistant lines, and suppressed tumor cell proliferation in vivo. Mechanistically, targeting of DECR1 caused cellular accumulation of linoleic acid, enhanced mitochondrial oxidative stress and lipid peroxidation, and ferroptosis. These findings implicate PUFA oxidation via DECR1 as a previously unexplored facet of FAO that promotes survival of PCa cells.
Combining machine learning and a universal acoustic feature-set yields efficient automated monitoring of ecosystems
Authors: Sethi Sarab S. , Jones Nick S. , Fulcher Ben D. , Picinali Lorenzo , Clink Dena J. , Klinck Holger , Orme C. David L. , Wrege Peter H. , Ewers Robert M.
Published: December 2019

Natural habitats are being impacted by human pressures at an alarming rate. Monitoring these ecosystem-level changes often requires labour-intensive surveys that are unable to detect rapid or unanticipated environmental changes. Here we developed a generalisable, data-driven solution to this challenge using eco-acoustic data. We exploited a convolutional neural network to embed ecosystem soundscapes from a wide variety of biomes into a common acoustic space. In both supervised and unsupervised modes, this allowed us to accurately quantify variation in habitat quality across space and in biodiversity through time. On the scale of seconds, we learned a typical soundscape model that allowed automatic identification of anomalous sounds in playback experiments, paving the way for real-time detection of irregular environmental behaviour including illegal activity. Our highly generalisable approach, and the common set of features, will enable scientists to unlock previously hidden insights from eco-acoustic data and offers promise as a backbone technology for global collaborative autonomous ecosystem monitoring efforts.
Dispersal behaviour as the outcome and trigger of multilevel selection in a social spider
Authors: Vásárhelyi Zsóka , Pruitt Jonathan N. , Scheuring István
Published: December 2019

The facultatively social spider Anelosimus studiosus offers a unique opportunity for understanding how multilevel selection acts in natural populations. However, the importance of previous empirical studies are shaded by a conceptual debate about whether colony-level selection is truly present in these populations or not. Here we introduce a detailed individual based model, where practically all assumptions are supported by empirical data. The only element of the female A. studiosus life cycle missing from the literature is how maturing female spiders decide whether to disperse. This behavioural component we estimate with evolutionary simulations. This model is able to recapitulate the characteristic size and composition distributions of natural populations in different environments. The evolutionary simulations revealed that the optimal dispersal behaviour of a maturing female varies both with her ecological environment and behavioural phenotype. This finding is open for straightforward empirical testing. In agreement with empirical findings we have established parameter ranges where the population is prone to extinction without multiple-female nests. We propose that the dispersal behaviour of individuals is both the result and the prerequisite of multilevel selection in this species.
Effect of pretreatment with different MMP inhibitors on shear bond strength of composite to primary teeth dentin after six months of aging
Authors: Parsaie Zahra , Mohammadi Najmeh , Firouzmandi Maryam
Published: December 2019

Background

loss of hybrid layer integrity compromises the resin-dentin bond stability. Subsequent release and activation of matrix metalloproteinase enzymes during dental restorative procedures or caries development are contributing factors to dentin-adhesive bond failure.

Aim

To investigate the effect of pre-treatment with different MMP inhibitors on the shear bond strength (SBS) of an etch-and-rinse adhesive (Adper Single Bond 2) to primary teeth dentin after six months of aging.

Methods

Sixty extracted anterior primary teeth, due to orthodontic reasons, were selected. A dentin block (6.0 mm × 6.0 mm × 2.0 mm) was obtained from each tooth. All the dentin blocks (n = 60) were pretreated for 60 s with either 0.01 M phosphate buffered saline (PBS, pH 7.2) in the control group, 2%: Chlorhexidine (CHX) solution, 2% Doxycycline (DO)solution and EDTA 17% after etching and before applying etch-and-rinse adhesive system (Adper Single Bond 2). Then composite was applied in clear teflon cylinders. The specimens were stored in artificial saliva for 6 months at 37°C and then the SBS values were determined with a universal testing machine. Representative samples were selected for visualization of the failure mode under stereomicroscope and SEM.

Results

No statistically significant difference observed between the SBS of the EDTA group, DO group and the control group (P value>0.05). CHX showed significantly higher SBS values compared to the other groups of the study after six months(P value=0.011).

Conclusion

Chlorhexidine significantly preserved the SBS of composite resin to deciduous dentin using etch and rinse adhesive Adper Single Bond 2 after 6 months of aging in artificial saliva.
Women and Men Were Proportionally Represented Among Speakers at Major National Neurology Conferences in 2017
Authors: McDermott Mollie , Burke James F. , McCalpin Haley , Shelgikar Anita V. , Gelb Douglas J. , Dunn Abbey , Beimer Nicholas J. , London Zachary N.
Published: December 2019

Objective

To determine whether speaking roles at five major neurology conferences in 2017 show disproportionate representation by men.

Methods

This study consisted of two cross-sectional analyses. In the first part, we compared speaker characteristics across meetings and by gender using descriptive statistics. In the second part, we linked presenters to the American Medical Association (AMA) Masterfile. For the primary analysis in the second part using linked AMA speaker data, we built models to estimate the influence of gender on speaker roles.

Results

1493 speakers were identified and included in our cross-sectional analysis. Women made up 28% of presenters from the US and 18% of presenters from other countries. After adjusting for years from medical school graduation and subspecialty, no effect of gender on speaker activity was observed (odds ratio [OR] for women 0.91; 95% confidence interval [CI], 0.77-1.07).

Conclusions

Factors aside from national conference speaking activity should be investigated to better understand sex differences in rank at top-ranked academic neurology programs.
A multiscale view of the Phanerozoic fossil record reveals the three major biotic transitions
Authors: Rojas Alexis , Calatayud Joaquin , Kowalewski Michal , Neuman Magnus , Rosvall Martin
Published: December 2019

The hypothesis of the Great Evolutionary Faunas is a foundational concept of macroevolutionary research postulating that three global mega-assemblages have dominated Phanerozoic oceans following abrupt biotic transitions. Empirical estimates of this large-scale pattern depend on several methodological decisions and are based on approaches unable to capture multiscale dynamics of the underlying Earth-Life System. Combining a multilayer network representation of fossil data with a multilevel clustering that eliminates the subjectivity inherent to distance-based approaches, we demonstrate that Phanerozoic oceans sequentially harbored four global benthic mega-assemblages. Shifts in dominance patterns among these global marine mega-assemblages are abrupt (end-Cambrian 494 Ma; end-Permian 252 Ma) or protracted (mid-Cretaceous 129 Ma), and represent the three major biotic transitions in Earth’s history. This finding suggests that the mid-Cretaceous radiation of the so-called Modern evolutionary Fauna, concurrent with gradual ecological changes associated with the Mesozoic Marine Revolution, triggered a biotic transition comparably to the transition following the largest extinction event in the Phanerozoic. Overall, our study supports the notion that both long-term ecological changes and major geological events have played crucial roles in shaping mega-assemblages that dominated Phanerozoic oceans.
Whole genome sequencing of Herpes Simplex Virus 1 directly from human cerebrospinal fluid reveals selective constraints in neurotropic viruses
Authors: Lassalle Florent , Beale Mathew A , Bharucha Tehmina , Williams Charlotte A , Williams Rachel J , Cudini Juliana , Goldstein Richard , Haque Tanzina , Depledge Daniel P , Breuer Judith
Published: December 2019

Herpes Simplex Virus type 1 (HSV-1) chronically infects over 70% of the global population. Clinical manifestations are largely restricted to recurrent epidermal vesicles. However, HSV-1 also leads to encephalitis, the infection of the brain parenchyma, with high associated rates of mortality and morbidity. In this study, we performed target enrichment followed by direct sequencing of HSV-1 genomes, using target enrichment methods on the cerebrospinal fluid (CSF) of clinical encephalitis patients and from skin swabs of epidermal vesicles on non-encephalopathic patients. Phylogenetic analysis revealed high inter-host diversity and little population structure. By contrast, samples from different lesions in the same patient clustered with similar patterns of allelic variants. Comparison of consensus genome sequences shows HSV-1 has been freely recombining, except for distinct islands of linkage disequilibrium (LD). This suggests functional constraints prevent recombination between certain genes, notably those encoding pairs of interacting proteins. Distinct LD patterns characterised subsets of viruses recovered from CSF and skin lesions, which may reflect different evolutionary constraints in different body compartments. Functions of genes under differential constraint related to immunity or tropism and provide new hypotheses on tissue-specific mechanisms of viral infection and latency.
Competition between kinesin-1 and myosin-V defineDrosophilaposterior determination
Authors: Lu Wen , Lakonishok Margot , Liu Rong , Billington Neil , Rich Ashley , Glotzer Michael , Sellers James R. , Gelfand Vladimir I.
Published: December 2019

Local accumulation ofoskar (osk) mRNA in theDrosophilaoocyte determines the posterior pole of the future embryo. Two major cytoskeletal components, microtubules and actin filaments, together with a microtubule motor, kinesin-1, and an actin motor, myosin-V, are essential foroskmRNA posterior localization. In this study, we use Staufen, an RNA-binding protein that colocalizes withoskmRNA, as a proxy for posterior determination. We demonstrate that posterior localization ofosk/Staufen is determined by competition between kinesin-1 and myosin-V. While kinesin-1 removesosk/Staufen from the cortex along microtubules, myosin-V anchorsosk/Staufen at the cortex. Myosin-V wins over kinesin-1 at the posterior pole due to low microtubule density at this site, while kinesin-1 wins it at anterior and lateral positions because they have high density of cortically-anchored microtubules. As a result, posterior determinants are removed from the anterior and lateral cortex but retained at the posterior pole. Thus, posterior determination ofDrosophilaoocyte is defined by kinesin-myosin competition, whose outcome is primarily determined by cortical microtubule density.
Riverscape genetics in brook lamprey: genetic diversity is less influenced by river fragmentation than by gene flow with the anadromous ecotype
Authors: Rougemont Quentin , Dolo Victoria , Oger Adrien , Besnard Anne-Laure , Huteau Dominique , Coutellec Marie-Agnès , Perrier Charles , Launey Sophie , Evanno Guillaume
Published: December 2019

Understanding the effect of human induced landscape fragmentation on gene flow and evolutionary potential of wild populations has become a major concern. Here, we investigated the effect of riverscape fragmentation on patterns of genetic diversity in the freshwater resident brook lamprey (Lampetra planeri) that has a low ability to pass obstacles to migration. We also tested the hypotheses of i) asymmetric gene flow following water current and ii) admixture with the closely related anadromousL. fluviatilisecotype having a positive effect onL. planerigenetic diversity. We genotyped 2472 individuals, including 225L. fluviatilis, sampled in 81 sites upstream and downstream from barriers to migration, in 29 West-European rivers. Linear modelling revealed a strong positive relationship between the distance to the source and genetic diversity, consistent with expected patterns of decreased gene flow into upstream populations. However, the presence of anthropogenic barriers had a moderate effect on spatial genetic structure. Accordingly, we found evidence for downstream-directed gene flow, supporting the hypothesis that barriers do not limit dispersal following water flow. DownstreamL. planeripopulations in sympatry withL. fluviatilisdisplayed consistently higher genetic diversity. We conclude that genetic drift and slight downstream gene flow mainly drive the genetic make up of upstreamL. planeripopulations whereas admixture between ecotypes maintains higher levels of genetic diversity inL. planeripopulations sympatric withL. fluviatilis. We discuss the implications of these results for the design of conservation strategies of lamprey, and other freshwater organisms with several ecotypes, in fragmented dendritic river networks.
Golgi outposts locally regulate microtubule orientation in neurons but are not required for the overall polarity of the dendritic cytoskeleton
Authors: Yang Sihui Z. , Wildonger Jill
Published: December 2019

Microtubule-organizing centers (MTOCs) often play a central role in organizing the cellular microtubule networks that underlie cell function. In neurons, microtubules in axons and dendrites have distinct polarities. Dendrite-specific Golgi outposts, in particular multi-compartment outposts, have emerged as regulators of acentrosomal microtubule growth, raising the question of whether outposts contribute to establishing the overall polarity of the dendritic microtubule cytoskeleton. Thecis-Golgi matrix protein GM130 has roles in both the MTOC activity of Golgi and in connecting Golgi compartments to form multi-compartment units. Using a combination of genetic approaches and live imaging in a Drosophila model, we found that GM130 is not essential for the overall polarity of the dendritic microtubule cytoskeleton. However, the mislocalization of multi-compartment Golgi outposts to axons disrupts the uniform orientation of axonal microtubules. This suggests that outposts have the capacity to influence microtubule polarity and, as our data indicate, likely do so independently of microtubule nucleation mediated by the γ-tubulin ring complex (γ-TuRC). Altogether, our results are consistent with the model that multi-compartment Golgi outposts may locally influence microtubule polarity, but that outposts are not necessary for the overall polarity of the dendritic microtubule cytoskeleton.
Why some size illusions affect grip aperture
Authors: Smeets Jeroen B.J. , Kleijn Erik , van der Meijden Marlijn , Brenner Eli
Published: December 2019

There is an extensive literature debating whether perceived size is used to guide grasping. A possible reason for not using judged size is that using judged positions might lead to more precise movements. As this argument does not hold for small objects, and all studies showing an effect of the Ebbinghaus illusion on grasping used small objects, we hypothesized that size information is used for small objects but not for large ones. Using a modified diagonal illusion, we obtained an effect of about 10% on perceptual judgements, without an effect on grasping, irrespective of object size. We therefore reject our precision hypothesis. We discuss the results in the framework of grasping as moving digits to positions on an object. We conclude that the reported disagreement on the effect of illusions is because the Ebbinghaus illusion not only affects size, but –unlike most size illusions– also affects perceived positions.
Trehalose as an alternative to glycerol as a glassing agent for in vivo DNP MRI
Authors: Brender Jeffrey R. , Kishimoto Shun , Eaton Gareth R. , Eaton Sandra S. , Saida Yu , Krishna Murali C.
Published: December 2019

In dynamic nuclear polarization (DNP), the solutions of the hyperpolarizable molecule and the paramagnetic agent need to form a glass when frozen to attain significant levels of polarization in reasonable time periods. Molecules which do not form glasses by themselves are often mixed with excipients to form glasses. While glassing agents are often essential in DNP studies, they have the potential to perturb the metabolic measurements that are being studied. Glycerol, the glassing agent of choice for in vivo DNP studies, is effective at reducing ice crystal formation during freezing but is rapidly metabolized, potentially altering the redox and ATP balance of the system. As a biologically inert alternative to glycerol, we show here that 15–20 wt % trehalose yields a glass that polarizes samples more rapidly than the commonly used 60% wt formulation of glycerol and yields similar polarization levels within clinically relevant timeframes. Trehalose may be an attractive alternative to glycerol for situations where there may be concerns about glycerol’s glucogenic potential and possible alteration of the ATP/ADP and redox balance.
Identifying Brain Network Topology Changes in Task Processes and Psychiatric Disorders
Authors: Rezaeinia Paria , Fairley Kim , Pal Piya , Meyer François G. , Carter R. McKell
Published: December 2019

A central goal in neuroscience is to understand how dynamic networks of neural activity produce effective representations of the world. Advances in the theory of graph measures raise the possibility of elucidating network topologies central to the construction of these representations. We leverage a result from the description of lollipop graphs to identify an iconic network topology in functional magnetic resonance imaging data and characterize changes to those networks during task performance and in populations diagnosed with psychiatric disorders. During task performance, we find that task-relevant subnetworks change topology, becoming more integrated by increasing connectivity throughout cortex. Analysis of resting-state connectivity in clinical populations shows a similar pattern of subnetwork topology changes; resting-scans becoming less default-like with more integrated sensory paths. The study of brain network topologies and their relationship to cognitive models of information processing raises new opportunities for understanding brain function and its disorders.

AUTHOR SUMMARY

Our mental lives are made up of a series of predictions about the world calculated by our brains. The calculations that produce these predictions are a result of how areas in our brain interact. Measures based on graph representations can make it clear what information can be combined and therefore help us better understand the computations the brain is performing. We make use of cutting-edge techniques that overcome a number of previous limitations to identify specific shapes in the functional brain network. These shapes are similar to hierarchical processing streams which play a fundamental role in cognitive neuroscience. The importance of these structures and the technique is highlighted by how they change under different task constraints and in individuals diagnosed with psychiatric disorders.
Use of dual electron probes reveals role of ferritin in erythropoiesis
Authors: Aronova Maria A. , Noh Seung-Jae , Zhang Guofeng , Byrnes Colleen , Meier Emily Riehm , Kim Young C. , Leapman Richard D.
Published: December 2019

Much is known about the finely regulated process of mammalian erythropoiesis that occurs in the bone marrow, whereby erythropoietic stem cells undergo terminal differentiation accompanied by enormous morphological changes to generate highly functional specialized red blood cells. However, a crucial step in erythropoiesis, the labile iron pool and its transport to mitochondria for heme production, is not well understood1. We apply a dual 3D imaging and spectroscopic technique, based on scanned electron probes, to measure distributions of ferritin iron-storage protein in ex vivo human erythropoietic stem cells, and to determine how those distributions change during terminal differentiation. After seven days of differentiation, the cells display a highly specialized architecture of organelles with anchored clustering of mitochondria and massive accumulation of Fe3+ in loaded ferritin cores localized to lysosomal storage depots, providing an iron source for heme production. Macrophages are not present in our ex vivo cultures, so they cannot be the source of the ferritin2. We suggest that lysosomal iron depots are required by developing reticulocytes while terminally differentiating and continuing to produce heme and globin, which assemble and concentrate to fill the cytoplasm after much of the cellular machinery is expelled.
Boldness and exploration vary between shell morphs but not environmental contexts in the snailCepaea nemoralis
Authors: Dahirel Maxime , Gaudu Valentin , Ansart Armelle
Published: December 2019

Understanding the maintenance of among-individual behavioral variation in populations, and predicting its consequences, are key challenges in behavioral ecology. Studying the association between repeatable behaviors and other traits under selection may shed light on the underlying selective pressures. We used the model snailCepaea nemoralisto examine whether individual behavior is associated with shell morph, a key trait that has been extensively studied in the context of thermal tolerance and predator avoidance, and which is known to be under strict genetic control in this species. We quantified proxies of boldness and exploration in snails of three morphs coming from two habitats with different thermal contexts. We show that both behaviors were repeatable at the among-individual level(within-stateRboldness= 0.22 [95% credible interval: 0.15, 0.29];Rexploration= 0.20 [0.15, 0.25]). Behavior was associated with shell morph, with the darker morph (five-banded) being consistently shyer and slower to explore. There was no evidence that thermal environment of origin influenced behavior. Snails became faster when test temperature increased; we found no evidence morphs differed in their thermal response. Boldness and exploration were correlated among individuals, forming a syndrome (r= 0.28 [0.10, 0.46]). We discuss what these results may tell us about the type of selection exerted by predators. We also detail how our results hint to a genetic link between shell morph and behavior, and the evolutionary implications of such a link. Finally, we discuss how our findings combined with decades of evolutionary research makeC. nemoralisa very valuable model to study the evolution of behavior in response to environmental changes.
The ER cargo receptor SURF4 facilitates efficient erythropoietin secretion
Authors: Lin Zesen , King Richard , Tang Vi , Myers Greggory , Balbin-Cuesta Ginette , Friedman Ann , McGee Beth , Desch Karl , Ozel Ayse Bilge , Siemieniak David , Reddy Pavan , Emmer Brian , Khoriaty Rami
Published: December 2019

Erythropoietin (EPO), a glycoprotein produced by specialized peritubular fibroblasts in the kidney, is the master regulator of erythropoiesis. EPO is secreted into the plasma in response to tissue hypoxia and stimulates erythroid differentiation and maturation. Though the transcriptional regulation of EPO has been well studied, the molecular determinants of EPO secretion remain unknown. Here, we generated a HEK293T reporter cell line that provides a quantifiable and selectable readout of intracellular EPO levels. Using this cell line, we performed a genome-scale CRISPR screen that identified SURF4 as an important mediator of EPO secretion. TargetingSURF4with multiple independent sgRNAs resulted in intracellular accumulation and extracellular depletion of EPO. Both of these phenotypes were rescued by expression ofSURF4cDNA. Additionally, consistent with a role for SURF4 as an ER cargo receptor of EPO, we found that disruption of SURF4 resulted in accumulation of EPO in the ER compartment, and that SURF4 and EPO physically interact. Furthermore, SURF4 disruption in Hep3B cells also caused a defect in the secretion of endogenous EPO, ruling out an artifact of heterologous overexpression. This work suggests that SURF4 functions as an ER cargo receptor that mediates the efficient secretion of EPO. Our findings also suggest that modulating SURF4 may be an effective treatment for disorders of erythropoeisis that are driven by aberrant EPO levels. Finally, we show that SURF4 overexpression results in increased secretion of EPO, suggesting a new strategy for more efficient production of recombinant EPO.
‘Awake delta’ and theta-rhythmic hippocampal network modes during intermittent locomotor behaviors in the rat
Authors: Schultheiss Nathan W. , Schlecht Maximillian , Jayachandran Maanasa , Brooks Deborah R. , McGlothan Jennifer L. , Guilarte Tomás R. , Allen Timothy A.
Published: December 2019

Delta-frequency network activity is commonly associated with sleep or behavioral disengagement accompanied by a dearth of cortical spiking, but delta in awake behaving animals is not well understood. We show that hippocampal (HC) synchronization in the delta frequency band (1-4 Hz) is related to animals’ locomotor behavior using a detailed analysis of simultaneous head- and body-tracking data. In contrast to running-speed modulation of the theta rhythm (6-10 Hz, a critical mechanism in navigation models), we observed that strong delta synchronization occurred when animals were stationary or moving slowly and while theta and fast gamma (55-120 Hz) were weak. We next combined time-frequency decomposition of the local field potential with hierarchical clustering algorithms to categorize momentary estimations of the power spectral density (PSD) into putative modes of HC activity. Delta and theta power measures from these modes were notably orthogonal, and theta and delta coherences between HC recording sites were monotonically related to theta-delta ratios across modes. Next, we focused on bouts of precisely-defined running and stationary behavior. Extraction of delta and theta power density estimates for each instance of these bout types confirmed the orthogonality between frequency bands seen across modes. We found that delta-band and theta-band coherence within HC, and in a small sample, between HC and medial prefrontal cortex (mPFC), mirrored delta and theta components of the PSD. Delta-band synchronization often developed rapidly when animals paused briefly between runs, as well as appearing throughout longer stationary bouts. Taken together, our findings suggest that delta-dominated network modes (and corresponding mPFC-HC couplings) represent functionally-distinct circuit dynamics that are temporally and behaviorally interspersed amongst theta-dominated modes during navigation. As such these modes of mPFC-HC circuit dynamics could play a fundamental role in coordinating encoding and retrieval mechanisms or decision-making processes at a timescale that segments event sequences within behavioral episodes.
Mental state space visualization for interactive modeling of personalized BCI control strategies
Authors: Kuzovkin Ilya , Tretyakov Konstantin , Uusberg Andero , Vicente Raul
Published: December 2019

Objective

Numerous studies in the area of BCI are focused on the search for a better experimental paradigm – a set of mental actions that a user can evoke consistently and a machine can discriminate reliably. Examples of such mental activities are motor imagery, mental computations, etc. We propose a technique that instead allows the user to try different mental actions in the search for the ones that will work best.

Approach

The system is based on a modification of the self-organizing map (SOM) algorithm and enables interactive communication between the user and the learning system through a visualization of user’s mental state space. During the interaction with the system the user converges on the paradigm that is most efficient and intuitive for that particular user.

Main results

Results of the two experiments, one allowing muscular activity, another permitting mental activity only, demonstrate soundness of the proposed method and offer preliminary validation of the performance improvement over the traditional closed-loop feedback approach.

Significance

The proposed method allows a user to visually explore their mental state space in real time, opening new opportunities for scientific inquiry. The application of this method to the area of brain-computer interfaces enables more efficient search for the mental states that will allow a user to reliably control a BCI system.
FUNCTIONAL NETWORK CONNECTIVITY (FNC)-BASED GENERATIVE ADVERSARIAL NETWORK (GAN) AND ITS APPLICATIONS IN CLASSIFICATION OF MENTAL DISORDERS
Authors: Zhao Jianlong , Zhi Dongmei , Yan Weizheng , Calhoun Vince D. , Sui Jing
Published: December 2019

Functional network connectivity (FNC) obtained from resting-state functional magnetic resonance imaging (fMRI) data have been commonly used to study mental disorders in neuroimaging applications. Likewise, generative adversarial networks (GANs) have performed well in multiple classification benchmark tasks. However, the application of GANs to fMRI is relatively rare. In this work, we proposed an FNC-based GAN for classifying brain disorders from healthy controls (HCs), in which FNC matrices were calculated by correlation of time courses derived from non-artefactual fMRI independent components (ICs). The proposed GAN model consisted of one discriminator (real FNCs) and one generator (fake FNCs), each has four fully-connected layers, and feature matching was implemented between each other to improve classification performance. An average accuracy of 70.1% with 10-fold cross-validation was achieved for classifying 269 major depressive disorder (MDD) patients from 286 HCs, at least 5.9% higher compared to other 6 popular classification approaches (54.5-64.2%). In another application to discriminating between 558 schizophrenia patients and 542 HCs from 7 sites, the proposed GAN model achieved 80.7% accuracy in leave-one-site-out prediction, outperforming support vector machine (SVM) and deep neural net (DNN) by 3-6%. To the best of our knowledge, this is the first attempt to apply GAN model based on fMRI data for mental disorder classification. Such a framework promises wide utility and great potential in neuroimaging biomarker identification.
Thiamine pyrophosphate riboswitches inBacteroidesspecies regulate transcription or translation of thiamine transport and biosynthesis genes
Authors: Costliow Zachary A. , Degnan Patrick H. , Vanderpool Carin K.
Published: December 2019

Thiamine (vitamin B1) and its phosphorylated precursors are necessary for decarboxylation reactions required in carbohydrate and branched chain amino acid metabolism. Due to its critical roles in central metabolism, thiamine is essential for human and animal hosts and their resident gut microbes. However, little is known about how thiamine availability shapes the composition of gut microbial communities and the physiology of individual species within those communities. Our previous work has implicated both thiamine biosynthesis and transport activities in the fitness ofBacteroidesspecies. To better understand thiamine-dependent gene regulation inBacteroides, we examined thiamine biosynthesis and transport genes in three representative species:Bacteroides thetaiotaomicron, Bacteroides uniformis, andBacteroides vulgatus. All three species possess thiamine biosynthetic operons controlled by highly conservedcis-acting thiamine pyrophosphate (TPP) riboswitches.B. thetaiotaomicronandB. uniformishave additional TPP riboswitch-controlled operons encoding thiamine transport functions. Transcriptome analyses showed that eachBacteroidesspecies had a distinct transcriptional response to exogenous thiamine. Analysis of transcript levels and translational fusions demonstrated that inB. thetaiotaomicron, the TPP riboswitch upstream of biosynthesis genes acts at the level of transcription, while TPP riboswitches upstream of transport operons work at the level of translation. InB. uniformisandB. vulgatus, TPP riboswitches work at the transcriptional level to control downstream operons. The varying responses to exogenous thiamine and use of varied regulatory mechanisms may play an important role in niche establishment by the Bacteroidetes in the complex and constantly shifting gut environment.

Importance

Bacteroidesspecies are important and abundant members of human gut microbiome communities. Their activities in the gut are influenced by constant changes in nutrient availability. In this study, we investigated the genetic basis of thiamine (Vitamin B1) uptake and biosynthesis in three representativeBacteroidesspecies. We found species-specific differences in the response to exogenous thiamine, and distinct mechanisms for regulation of uptake and biosynthesis gene expression. Our work implies that gutBacteroideshave evolved distinct strategies for making or acquiring an essential nutrient. These mechanisms may play an important role in the success ofBacteroidesin establishing a niche within complex gut microbiome communities.
High-pressure polymorphism in pyridine
Authors: Giordano Nico , Beavers Christine M. , Campbell Branton J. , Eigner Václav , Gregoryanz Eugene , Marshall Willliam G. , Peña-Álvarez Miriam , Teat Simon J. , Vennari Cara E. , Parsons Simon
Published: December 2019

Single crystals of the high-pressure phases II and III of pyridine have been obtained by in situ crystallization at 1.09 and 1.69 GPa, revealing the crystal structure of phase III for the first time using X-ray diffraction. Phase II crystallizes in P212121 with Z′ = 1 and phase III in P41212 with Z′ = ½. Neutron powder diffraction experiments using pyridine-d5 establish approximate equations of state of both phases. The space group and unit-cell dimensions of phase III are similar to the structures of other simple compounds with C
2v molecular symmetry, and the phase becomes stable at high pressure because it is topologically close-packed, resulting in a lower molar volume than the topologically body-centred cubic phase II. Phases II and III have been observed previously by Raman spectroscopy, but have been mis-identified or inconsistently named. Raman spectra collected on the same samples as used in the X-ray experiments establish the vibrational characteristics of both phases unambiguously. The pyridine molecules interact in both phases through CH...π and CH...N interactions. The nature of individual contacts is preserved through the phase transition between phases III and II, which occurs on decompression. A combination of rigid-body symmetry mode analysis and density functional theory calculations enables the soft vibrational lattice mode which governs the transformation to be identified.
Influence of the position of the methyl substituent and N-oxide formation on the geometry and intermolecular interactions of 1-(phenoxyethyl)piperidin-4-ol derivatives
Authors: Żesławska Ewa , Kalinowska-Tłuścik Justyna , Nitek Wojciech , Marona Henryk , Waszkielewicz Anna M.
Published: December 2019

Aminoalkanol derivatives have attracted much interest in the field of medicinal chemistry as part of the search for new anticonvulsant drugs. In order to study the influence of the methyl substituent and N-oxide formation on the geometry of molecules and intermolecular interactions in their crystals, three new examples have been prepared and their crystal structures determined by X-ray diffraction. 1-[(2,6-Dimethylphenoxy)ethyl]piperidin-4-ol, C15H23NO2, 1, and 1-[(2,3-dimethylphenoxy)ethyl]piperidin-4-ol, C15H23NO2, 2, crystallize in the orthorhombic system (space groups P212121 and Pbca, respectively), with one molecule in the asymmetric unit, whereas the N-oxide 1-[(2,3-dimethylphenoxy)ethyl]piperidin-4-ol N-oxide monohydrate, C15H23NO3·H2O, 3, crystallizes in the monoclinic space group P21/c, with one N-oxide molecule and one water molecule in the asymmetric unit. The geometries of the investigated compounds differ significantly with respect to the conformation of the O—C—C linker, the location of the hydroxy group in the piperidine ring and the nature of the intermolecular interactions, which were investigated by Hirshfeld surface and corresponding fingerprint analyses. The crystal packing of 1 and 2 is dominated by a network of O—H...N hydrogen bonds, while in 3, it is dominated by O—H...O hydrogen bonds and results in the formation of chains.
One-pot concomitant preparation of two copper(II) coordination polymers with different configurations of bridging bithiophene ligands
Authors: Shi Zhi-Qiang , Ji Ning-Ning , Hu Hai-Liang
Published: December 2019

By employing the conjugated bithiophene ligand 5,5′-bis(1H-imidazol-1-yl)-2,2′-bithiophene (bibp), which can exhibit trans and cis conformations, two different CuII coordination polymers, namely, poly[[μ-5,5′-bis(1H-imidazol-1-yl)-2,2′-bithiophene-κ2
N:N′](μ2-4,4′-oxydibenzoato-κ2
O:O′)copper(II)], [Cu(C14H8O5)(C14H10N4S2)]
n
or [Cu(bibp)(oba)]
n
, (I), and catena-poly[μ-aqua-bis[μ-5,5′-bis(1H-imidazol-1-yl)-2,2′-bithiophene-κ2
N:N′]bis(μ3-4,4′-oxydibenzoato)-κ3
O:O′:O′′;κ4
O:O′,O′′:O′-dicopper(II)], [Cu2(C14H8O5)2(C14H10N4S2)(H2O)]
n
or [Cu2(bibp)(oba)2(H2O)]
n
, (II), have been prepared through one-pot concomitant crystallization and characterized by single-crystal X-ray diffraction, IR spectroscopy, elemental analysis, powder X-ray diffraction (PXRD) and thermogravimetric (TG) analysis. Single-crystal X-ray diffraction indicates that the most interesting aspect of the structure is the existence of sole trans and cis conformations of the bibp ligand in a single net of (I) and (II), respectively. Compound (I) displays a threefold interpenetrating three-dimensional framework with a 4-connected {65.8} cds topology, whereas (II) features a one-dimensional chain structure. In the crystal of (II), the polymeric chains are further extended through C—H...O hydrogen bonds and C—H...π interactions into a three-dimensional supramolecular architecture. In addition, strong intramolecular O—H...O hydrogen bonds formed between the bridging water molecules and the carboxylate O atoms improve the stability of the framework of (II). Furthermore, solid-state UV–Vis spectroscopy experiments show that compounds (I) and (II) exhibit optical band gaps which are characteristic for optical semiconductors, with values of 2.70 and 2.26 eV, respectively.
Solid-state conformations of linear depsipeptide amides with an alternating sequence of α,α-disubstituted α-amino acid and α-hydroxy acid
Authors: Linden Anthony , Magirius J. E. Florian , Heimgartner Heinz
Published: December 2019

Depsipeptides and cyclodepsipeptides are analogues of the corresponding peptides in which one or more amide groups are replaced by ester functions. Reports of crystal structures of linear depsipeptides are rare. The crystal structures and conformational analyses of four depsipeptides with an alternating sequence of an α,α-disubstituted α-amino acid and an α-hydroxy acid are reported. The molecules in the linear hexadepsipeptide amide in (S)-Pms-Acp-(S)-Pms-Acp-(S)-Pms-Acp-NMe2 acetonitrile solvate, C47H58N4O9·C2H3N, (3b), as well as in the related linear tetradepsipeptide amide (S)-Pms-Aib-(S)-Pms-Aib-NMe2, C28H37N3O6, (5a), the diastereoisomeric mixture (S,R)-Pms-Acp-(R,S)-Pms-Acp-NMe2/(R,S)-Pms-Acp-(R,S)-Pms-Acp-NMe2 (1:1), C32H41N3O6, (5b), and (R,S)-Mns-Acp-(S,R)-Mns-Acp-NMe2, C30H37N3O6, (5c) (Pms is phenyllactic acid, Acp is 1-aminocyclopentanecarboxylic acid and Mns is mandelic acid), generally adopt a β-turn conformation in the solid state, which is stabilized by intramolecular N—H...O hydrogen bonds. Whereas β-turns of type I (or I′) are formed in the cases of (3b), (5a) and (5b), which contain phenyllactic acid, the torsion angles for (5c), which incorporates mandelic acid, indicate a β-turn in between type I and type III. Intermolecular N—H...O and O—H...O hydrogen bonds link the molecules of (3a) and (5b) into extended chains, and those of (5a) and (5c) into two-dimensional networks.
A Co-MOF with a (4,4)-connected binodal two-dimensional topology: synthesis, structure and photocatalytic properties
Authors: Wang Zhi-Xiang , Tian Hai-Xin , Ding Jian-Gang , Li Bao-Long , Wu Bing
Published: December 2019

The Co-MOF poly[[diaqua{μ4-1,1,2,2-tetrakis[4-(1H-1,2,4-triazol-1-yl)phenyl]ethylene-κ4
N:N′:N′′:N′′′}cobalt(II)] benzene-1,4-dicarboxylic acid benzene-1,4-dicarboxylate], {[Co(C34H24N12)(H2O)2](C8H4O4)·C8H6O4}
n
or {[Co(ttpe)(H2O)2](bdc)·(1,4-H2bdc)}
n
, (I), was synthesized by the hydrothermal method using 1,1,2,2-tetrakis[4-(1H-1,2,4-triazol-1-yl)phenyl]ethylene (ttpe), benzene-1,4-dicarboxylic acid (1,4-H2bdc) and Co(NO3)2·6H2O, and characterized by single-crystal X-ray diffraction, IR spectroscopy, powder X-ray diffraction (PXRD), luminescence, optical band gap and valence band X-ray photoelectron spectroscopy (VB XPS). Co-MOF (I) shows a (4,4)-connected binodal two-dimensional topology with a point symbol of {44·62}{44·62}. The two-dimensional networks capture free neutral 1,4-H2bdc molecules and bdc2− anions, and construct a three-dimensional supramolecular architecture via hydrogen-bond interactions. MOF (I) is a good photocatalyst for the degradation of methylene blue and rhodamine B under visible-light irradiation and can be reused at least five times.
Crystal structure, Hirshfeld analysis and a molecular docking study of a new inhibitor of the Hepatitis B virus (HBV): ethyl 5-methyl-1,1-dioxo-2-{[5-(pentan-3-yl)-1,2,4-oxadiazol-3-yl]methyl}-2H-1,2,6-thiadiazine-4-carboxylate
Authors: Ivachtchenko Alexandre V. , Kovalenko Sergiy M. , Kravchenko Dmitry V. , Mitkin Oleg D. , Ivanov Vladimir V. , Langer Thierry
Published: December 2019

The title compound, C15H22N4O5S, was prepared via alkylation of 3-(chloromethyl)-5-(pentan-3-yl)-1,2,4-oxadiazole in anhydrous dioxane in the presence of triethylamine. The thiadiazine ring has an envelope conformation with the S atom displaced by 0.4883 (6) Å from the mean plane through the other five atoms. The planar 1,2,4-oxadiazole ring is inclined to the mean plane of the thiadiazine ring by 77.45 (11)°. In the crystal, molecules are linked by C—H...N hydrogen bonds, forming chains propagating along the b-axis direction. Hirshfeld surface analysis and two-dimensional fingerprint plots have been used to analyse the intermolecular contacts present in the crystal. Molecular docking studies were use to evaluate the title compound as a potential system that interacts effectively with the capsid of the Hepatitis B virus (HBV), supported by an experimental in vitro HBV replication model.
Crystal structures of three 6-aryl-2-(4-chlorobenzyl)-5-[(1H-indol-3-yl)methyl]imidazo[2,1-b][1,3,4]thiadiazoles
Authors: Shamanth Sadashivamurthy , Mantelingu Kempegowda , Kiran Kumar Haruvegowda , Yathirajan Hemmige S. , Foro Sabine , Glidewell Christopher
Published: December 2019

Three title compounds, namely, 2-(4-chlorobenzyl)-5-[(1H-indol-3-yl)methyl]-6-phenylimidazo[2,1-b][1,3,4]thiadiazole, C26H19ClN4S, (I), 2-(4-chlorobenzyl)-6-(4-fluorophenyl)-5-[(1H-indol-3-yl)methyl]imidazo[2,1-b][1,3,4]thiadiazole, C26H18ClFN4S, (II), and 6-(4-bromophenyl)-2-(4-chlorobenzyl)-5-[(1H-indol-3-yl)methyl]imidazo[2,1-b][1,3,4]thiadiazole, C26H18BrClN4S, (III), have been prepared using a reductive condensation of indole with the corresponding 6-aryl-2-(4-chlorobenzyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehydes (aryl = phenyl, 4-fluorophenyl or 4-bromophenyl), and their crystal structures have been determined. The asymmetric unit of compound (I) consists of two independent molecules and one of the molecules exhibits disorder of the 4-chlorobenzyl substituent with occupancies 0.6289 (17) and 0.3711 (17). Each type of molecule forms a C(8) chain motif built from N—H...N hydrogen bonds, which for the fully ordered molecule is reinforced by C—H...π interactions. In compound (II), the chlorobenzyl unit is again disordered, with occupancies 0.822 (6) and 0.178 (6), and the molecules form C(8) chains similar to those in (I), reinforced by C—H...π interactions involving only the major disorder component. The chlorobenzyl unit in compound (III) is also disordered with occupancies of 0.839 (5) and 0.161 (5). The molecules are linked by a combination of one N—H...N hydrogen bond and four C—H...π interactions, forming a three-dimensional framework.
Di-μ3-chlorido-tetra-μ2-chlorido-dichloridotetrakis(N,N-diethylethane-1,2-diamine-κ2
N,N′)tetracadmium(II)
Authors: Al-Sudani Abdul-Razak H. , Abdulridha Myasim Qasim , Kariuki Benson M.
Published: December 2019

In the title compound, [Cd4Cl8(C6H16N2)4], the Cd2+ cations and Cl− anions form M
4Cl8 clusters with six of the Cl− ions bridging Cd2+ cations and two being pendant. Each Cd2+ cation has distorted octahedral coordination completed by four Cl− ions and two N atoms of the asymmetrical bidentate amino ligand. The cluster consists of pairs of face-sharing hexahedra linked by a shared edge.