bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling brain dynamics after tumor resection using The Virtual Brain
Authors: Aerts Hannelore , Schirner Michael , Dhollander Thijs , Jeurissen Ben , Achten Eric , Van Roost Dirk , Ritter Petra , Marinazzo Daniele 
Published: September 2019

AbstractBrain tumor patients scheduled for tumor resection often face significant uncertainty, as the outcome of neurosurgery is difficult to predict at the individual patient level. Recently, computational modeling of brain activity using so-called brain network models has been introduced as a promising tool for this purpose. However, brain network models first have to be validated, before they can be used to predict brain dynamics. In prior work, we optimized individual brain network model parameters to maximize the fit with empirical brain activity. In this study, we extend this line of research by examining the stability of fitted parameters before and after tumor resection, and compare it with baseline parameter variability using data from healthy control subjects. Based on these findings, we perform the first “virtual neurosurgery” analyses to evaluate the potential of brain network modeling in predicting brain dynamics after tumor resection.We find that brain network model parameters are relatively stable over time in brain tumor patients who underwent tumor resection, compared with baseline variability in healthy control subjects. In addition, we identify several robust associations between individually optimized model parameters, structural network topology and cognitive performance from pre-to post-operative assessment. Concerning the virtual neurosurgery analyses, we obtain promising results in some patients, whereas the predictive accuracy of the currently applied model is poor in others. These findings reveal interesting avenues for future research, as well as important limitations that warrant further investigation.
Discovery and evaluation of a novel step in the flavonoid biosynthesis pathway regulated by F3H gene using a yeast expression system
Authors: Jan Rahmatullah , Asaf Sajjad , Paudel Sanjita , Lee Sangkyu , Kim Kyung-Min 
Published: September 2019

AbstractKaempferol and quercetin are the essential plant secondary metabolites that confer huge biological functions in the plant defense system. These metabolites are produced in low quantities in plants, therefore engineering microbial factory is a favorable strategy for the production of these metabolites. In this study, biosynthetic pathways for kaempferol and quercetin were constructed in Saccharomyces cerevisiae using naringenin as a substrate. The results elucidated a novel step for the first time in kaempferol and quercetin biosynthesis directly from naringenin catalyzed by flavonol 3-hydroxylase (F3H). F3H gene from rice was cloned into pRS42K yeast episomal plasmid (YEP) vector using BamH1 and Xho1 restriction enzymes. We analyzed our target gene activity in engineered and in empty strains. The results were confirmed through TLC followed by Western blotting, nuclear magnetic resonance (NMR), and LC-MS. TLC showed positive results on comparing both compounds extracted from the engineered strain with the standard reference. Western blotting confirmed lack of Oryza sativa flavonol 3-hydroxylase (OsF3H) activity in empty strains while high OsF3H expression in engineered strains. NMR spectroscopy confirmed only quercetin, while LCMS-MS results revealed that F3H is responsible for naringenin conversion to both kaempferol and quercetin. These results concluded that rice F3H catalyzes naringenin metabolism via hydroxylation and synthesizes kaempferol and quercetin.HighlightsCurrent study is a discovery of a novel step in flavonoid biosynthesis pathway of rice plant.In this study F3H gene from rice plant was functionally expressed in yeast expression system.Results confirmed that, F3H gene is responsible for the canalization of naringenin and converted into kaempferol and quercetin.The results were confirmed through, western blotting, TLC, HPLC and NMR analysis.
Type-specific dendritic integration in mouse retinal ganglion cells
Authors: Ran Yanli , Huang Ziwei , Baden Tom , Baayen Harald , Berens Philipp , Franke Katrin , Euler Thomas 
Published: September 2019

ABSTRACTNeural computation relies on the integration of synaptic inputs across a neuron’s dendritic arbour. However, the fundamental rules that govern dendritic integration are far from understood. In particular, it is still unclear how cell type-specific differences in dendritic integration arise from general features of neural morphology and membrane properties. Here, retinal ganglion cells (RGCs), which relay the visual system’s first computations to the brain, represent an exquisite model. They are functionally and morphologically diverse yet defined, and they allow studying dendritic integration in a functionally relevant context. Here, we show how four morphologically distinct types of mouse RGC with shared excitatory synaptic input (transient Off alpha, transient Off mini, sustained Off, and F-miniOff) exhibit distinct dendritic integration rules. Using two-photon imaging of dendritic calcium signals and biophysical modelling, we demonstrate that these RGC types strongly differ in their spatio-temporal dendritic integration: In transient Off alpha cells, dendritic receptive fields displayed little spatial overlap, indicative of a dendritic arbour that is partitioned in largely isolated regions. In contrast, dendritic receptive fields in the other three RGCs overlapped greatly and were offset to the soma, suggesting strong synchronization of dendritic signals likely due to backpropagation of somatic signals. Also temporal correlation of dendritic signals varied extensively among these types, with transient Off mini cells displaying the highest correlation across their dendritic arbour. Modelling suggests that morphology alone cannot explain these differences in dendritic integration, but instead specific combinations of dendritic morphology and ion channel densities are required. Together, our results reveal how neurons exhibit distinct dendritic integration profiles tuned towards their type-specific computations in their circuits, with the interplay between morphology and ion channel complement as a key contributor.
Contextual extinction of drug-associated discriminative stimuli fails to attenuate drug-vs-food choice in rhesus monkeys
Authors: Banks Matthew L , Hutsell Blake A. , Negus S Stevens 
Published: September 2019

ABSTRACTRelapse within the context of a substance use disorder can be triggered by cues that function as discriminative stimuli to signal contingencies of drug availability and promote drug-taking behavior. Extinction procedures can weaken this association between drug-associated cues and drug-taking behavior and may reduce the probability of relapse. This study evaluated a regimen of extinction training on cocaine and heroin self-administration in rhesus monkeys under a drug-vs.-food choice procedure. Behavior was initially maintained under a concurrent schedule of food (1-g food pellets; fixed-ratio 100 schedule) and cocaine injections (0-0.1 mg/kg/injection; fixed-ratio 10) (n=4 males) or heroin injections (0-0.01 mg/kg/injection; fixed-ratio 10) (n=3 females and 1 male) during daily 2-h choice sessions. Subsequently, choice sessions were supplemented by daily 20-h extinction sessions for 14 consecutive days. During extinction sessions, drug-associated discriminative stimuli were presented, but responding produced saline injections. Drug continued to be available during choice sessions. Prior to extinction, both cocaine- and heroin-maintained dose-dependent increases in drug-vs.-food choice. Exposure to 14 extinction sessions failed to significantly decrease drug choice and increase food choice. These preclinical results do not support the effectiveness of extinguishing drug-associated discriminative stimuli as a non-pharmacological treatment strategy for reducing drug choice.
Effects of Repeated Treatment with Monoamine-Transporter-Inhibitor Antidepressants on Pain-Related Depression of Intracranial Self-Stimulation in Rats
Authors: Legakis LP , Karim-Nejad L , Negus SS 
Published: September 2019

ABSTRACTSynaptic neurotransmission with dopamine (DA), norepinephrine (NE), and serotonin (5-HT) is terminated primarily by reuptake into the presynaptic terminal via the DA, NE, and 5-HT transporters (DAT/NET/SERT, respectively). Monoamine transporter inhibitors constitute one class of drugs used to treat pain, and emergence of analgesic effects by these compounds often requires repeated treatment for days or weeks. The present study compared antinociceptive effects produced by repeated treatment with monoamine transporter inhibitors in a preclinical assay of pain-related depression of positively reinforced operant responding. Adult male Sprague-Dawley rats equipped with microelectrodes targeting a brain-reward area responded for pulses of electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. Intraperitoneal injection of dilute lactic acid served as a noxious stimulus that repeatedly depressed ICSS and also produced weight loss during 7 days of repeated acid administration. Both acid-induced ICSS depression and weight loss were blocked by repeated pretreatment with the nonsteroidal anti-inflammatory drug ketorolac (a positive control) but not by the kappa opioid receptor agonist U69,593 (a negative control). Like ketorolac, the DAT/NET inhibitor bupropion fully blocked acid-induced ICSS depression and weight loss throughout all 7 days of treatment. Conversely, the NET-selective inhibitor nortriptyline and SERT-selective inhibitor citalopram produced antinociception only after several days of repeated treatment, and weight loss was attenuated by citalopram but not by nortriptyline. These results support effectiveness of bupropion to alleviate signs of pain-related behavioral depression in rats and further suggest that nortriptyline and citalopram produce a more gradual onset of antinociception during repeated treatment.
Divergent Cl− and H+ pathways underlie transport coupling and gating in CLC exchangers and channels
Authors: Leisle Lilia , Xu Yanyan , Fortea Eva , Galpin Jason , Vien Malvin , Ahern Christopher A. , Accardi Alessio , Bernèche Simon 
Published: September 2019

AbstractThe CLC family of anion transporting proteins is comprised of secondary active H+-coupled exchangers and of Cl− channels. Both functional subtypes play key roles in human physiology, and mutations causing their dysfunction lead to numerous genetic disorders. Current models suggest that the CLC exchangers do not utilize a classical ‘ping-pong’ mechanism of antiport, where the transporter sequentially interacts with one substrate at a time. Rather, in the CLC exchangers both substrates bind and translocate simultaneously while moving through partially congruent pathways. How ions of opposite electrical charge bypass each other while moving in opposite directions through a shared permeation pathway remains unknown. Here, we use MD simulations in combination with biochemical and electrophysiological measurements to identify a pair of highly conserved phenylalanine residues that form an aromatic pathway, separate from the Cl− pore, whose dynamic rearrangements enable H+ movement. Mutations of these aromatic residues impair H+ transport and voltage-dependent gating in the CLC exchangers. Remarkably, the role of the aromatic pathway is evolutionarily conserved in CLC channels. Using atomic-scale mutagenesis we show that the electrostatic properties and conformational flexibility of these aromatic residues are essential determinants of channel gating. Our results suggest that Cl− and H+ move through physically distinct and evolutionarily conserved routes through the CLC channels and transporters. We propose a unifying mechanism that describes the gating mechanism of CLC exchangers and channels.
Major histocompatibility complex class I-restricted protection against murine cytomegalovirus requires missing-self recognition by the natural killer cell inhibitory Ly49 receptors
Authors: Parikh Bijal A. , Bern Michael D. , Piersma Sytse J. , Yang Liping , Beckman Diana L. , Poursine-Laurent Jennifer , Douglas Beatrice Plougastel , Yokoyama Wayne M. 
Published: September 2019

AbstractViruses have evolved strategies that highlight critical, intertwined host immune mechanisms. As postulated by the missing-self hypothesis, natural killer (NK) cells and major histocompatibility complex class I (MHC-I)-restricted cytotoxic T lymphocytes (CTLs) have opposing requirements for ubiquitously expressed MHC-I molecules. Since NK cell MHC-I-specific Ly49 inhibitory receptors prevent killing of cells with normal MHC-I, viruses evading CTLs by down-regulating MHC-I should be vulnerable to NK cells. However, definitive integratedin vivoevidence for this interplay has been lacking, in part due to receptor polymorphism and a proposed second function of Ly49 receptors in licensing NK cells via self-MHC-I. Here we generated mice lacking specific Ly49 inhibitory receptors to show their essential role in licensing and controlling murine cytomegalovirus (MCMV) infectionin vivoin an MHC-restricted manner. When MCMV cannot down-regulate MHC-I, NK cells cannot control infection that instead is mediated by CTLs, as predicted by the missing-self hypothesis.
EnClaSC: A novel ensemble approach for accurate and robust cell-type classification of single-cell transcriptomes
Authors: Chen Xiaoyang , Chen Shengquan , Jiang Rui 
Published: September 2019

AbstractBackgroundIn recent years, the rapid development of single-cell RNA-sequencing (scRNA-seq) techniques enables the quantitative characterization of cell types at a single-cell resolution. With the explosive growth of the number of cells profiled in individual scRNA-seq experiments, there is a demand for novel computational methods for classifying newly-generated scRNA-seq data onto annotated labels. Although several methods have recently been proposed for the cell-type classification of single-cell transcriptomic data, such limitations as inadequate accuracy, inferior robustness, and low stability greatly limit their wide applications.ResultsWe propose a novel ensemble approach, named EnClaSC, for accurate and robust cell-type classification of single-cell transcriptomic data. Through comprehensive validation experiments, we demonstrate that EnClaSC can not only be applied to the self-projection within a specific dataset and the cell-type classification across different datasets, but also scale up well to various data dimensionality and different data sparsity. We further illustrate the ability of EnClaSC to effectively make cross-species classification, which may shed light on the studies in correlation of different species. EnClaSC is freely available at https://github.com/xy-chen16/EnClaSC.ConclusionsEnClaSC enables highly accurate and robust cell-type classification of single-cell transcriptomic data via an ensemble learning method. We expect to see wide applications of our method to not only transcriptome studies, but also the classification of more general data.
A rare opportunist,Morganella morganii, decreases severity of polymicrobial catheter-associated urinary tract infection
Authors: Learman Brian S. , Brauer Aimee L. , Eaton Kathryn A. , Armbruster Chelsie E. 
Published: September 2019

AbstractCatheter-associated urinary tract infections (CAUTIs) are common hospital-acquired infections and frequently polymicrobial, which complicates effective treatment. However, few studies experimentally address the consequences of polymicrobial interactions within the urinary tract, and the clinical significance of polymicrobial bacteriuria is not fully understood.Proteus mirabilisis one of the most common causes of monomicrobial and polymicrobial CAUTI, and frequently co-colonizes withEnterococcus faecalis, Escherichia coli, Providencia stuartii, andMorganella morganii. P. mirabilisinfections are particularly challenging due to its potent urease enzyme, which facilitates formations of struvite crystals, catheter encrustation, blockage, and formation of urinary stones. We previously determined that interactions betweenP. mirabilisand other uropathogens can enhanceP. mirabilisurease activity, resulting in greater disease severity during experimental polymicrobial infection. Our present work reveals thatM. morganiiacts onP. mirabilisin a contact-independent manner to decrease urease activity. Furthermore,M. morganiiactively prevents urease enhancement byE. faecalis, P. stuartii, andE. coli.Importantly, these interactions translate to modulation of disease severity during experimental CAUTI, predominantly through a urease-dependent mechanism. Thus, products secreted by multiple bacterial species in the milieu of the catheterized urinary tract can directly impact prognosis.
Apical length governs computational diversity of L5 pyramidal neurons
Authors: Galloni Alessandro R. , Laffere Aeron , Rancz Ede 
Published: September 2019

AbstractAnatomical similarity across the neocortex has led to the common assumption that the circuitry is modular and performs stereotyped computations. Layer 5 pyramidal neurons (L5PNs) in particular are thought to be central to cortical computation because of their extensive arborisation and nonlinear dendritic operations. Here, we demonstrate that computations associated with dendritic Ca2+ plateaus in L5PNs vary substantially between the primary and secondary visual cortices. L5PNs in the secondary visual cortex show reduced dendritic excitability and smaller propensity for burst firing. This reduced excitability is correlated with shorter apical dendrites. Using numerical modelling, we uncover a universal principle underlying the influence of apical length on dendritic backpropagation and excitability, based on a Na+ channel-dependent broadening of backpropagating action potentials. In summary, we provide new insights into the modulation of dendritic excitability by apical dendrite length and show that the operational repertoire of L5 neurons is not universal throughout the brain.
Frequency-dependent organization of the brain’s functional network through delayed-interactions
Authors: Ziaeemehr Abolfazl , Zarei Mina , Valizadeh Alireza , Mirasso Claudio R. 
Published: September 2019

AbstractThe structure of the brain network shows modularity at multiple spatial scales. The effect of the modular structure on the brain dynamics has been the focus of several studies in recent years but many aspects remain to be explored. For example, it is not well-known how the delays in the transmission of signals between the neurons and the brain regions, interact with the modular structure to determine the brain dynamics. In this paper, we show an important impact of the delays on the collective dynamics of the brain network with modular structure; that is, the degree of the synchrony between different brain regions is dependent on the frequency. In particular, we show that increasing the frequency the network transits from a global synchrony state to an asynchronous state, through a transition region over which the local synchrony inside the modules is stronger than the global synchrony. When the delays are dependent on the distance between the nodes, the modular structure of different spatial scales appears in the correlation matrix over different specific frequency bands, so that, finer spatial modular structure reveal in higher frequency bands. The results are justified by a simple theoretical argument and elaborated by simulations on several simplified modular networks and the connectome with different spatial resolutions.
Signals of anticipation of reward and of mean reward rates in the human brain
Authors: Viviani Roberto , Dommes Lisa , Bosch Julia , Steffens Michael , Paul Anna , Schneider Katharina L. , Stingl Julia C. , Beschoner Petra 
Published: September 2019

AbstractTheoretical models of dopamine function stemming from reinforcement learning theory have emphasized the importance of prediction errors, which signal changes in the expectation of impending rewards. Much less is known about the effects of mean reward rates, which may be of motivational significance due to their role in computing the optimal effort put into exploiting reward opportunities. Here, we used a reinforcement learning model to design three functional neuroimaging studies and disentangle the effects of changes in reward expectations and mean reward rates, showing recruitment of specific regions in the brainstem regardless of prediction errors. While changes in reward expectations activated ventral striatal areas as in previous studies, mean reward rates preferentially modulated the substantia nigra/ventral tegmental area, deep layers of the superior colliculi, and a posterior pontomesencephalic region. These brainstem structures may work together to set motivation and attentional efforts levels according to perceived reward opportunities.
Effects of enriched housing on the neuronal morphology of mice that lack zinc transporter 3 (ZnT3) and vesicular zinc
Authors: McAllister Brendan B. , Thackray Sarah E. , de la Orta Brenda Karina Garciá , Gosse Elise , Tak Purnoor , Chipak Colten , Rehal Sukhjinder , Rascón Abril Valverde , Dyck Richard H. 
Published: September 2019

ABSTRACTIn the central nervous system, certain neurons store zinc within the synaptic vesicles of their axon terminals. This vesicular zinc can then be released in an activity-dependent fashion as an intercellular signal. The functions of vesicular zinc are not entirely understood, but evidence suggests that it is important for some forms of experience-dependent plasticity in the brain. The ability of neurons to store and release vesicular zinc is dependent on expression of the vesicular zinc transporter, ZnT3. Here, we examined the neuronal morphology of mice that lack ZnT3. Brains were collected from mice housed under standard laboratory conditions and from mice housed in enriched environments – large, multilevel enclosures with running wheels, numerous objects and tunnels, and a greater number of cage mates. Golgi-Cox staining was used to visualize neurons for analysis of dendritic length and dendritic spine density. Neurons were analyzed from the barrel cortex, striatum, basolateral amygdala, and hippocampus (CA1). ZnT3 knockout mice, relative to wild type mice, exhibited increased basal dendritic length in the layer 2/3 pyramidal neurons of barrel cortex, independently of housing condition. Environmental enrichment decreased apical dendritic length in these same neurons and increased dendritic spine density on striatal medium spiny neurons. Elimination of ZnT3 did not modulate any of the effects of enrichment. Our results provide no evidence that vesicular zinc is required for the experience-dependent changes that occur in response to environmental enrichment. They are consistent, however, with recent reports suggesting increased cortical volume in ZnT3 knockout mice.