bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Vasoconstriction And Volume Expansion on Veno-Arterial ECMO Flow
Authors: Moller Per W. , Hana Anisa , Heinisch Paul Philipp , Liu Shengchen , Djafarzadeh Siamak , Haenggi Matthias , Bloch Andreas , Takala Jukka , Jakob Stephan M. , Berger David 
Published: June 2018

ABSTRACT

Background:
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is gaining widespread use in the treatment of severe cardiorespiratory failure. Blood volume expansion is commonly used to increase ECMO flow (QECMO), with risk of positive fluid balance and worsening prognosis. We studied the effects of vasoconstriction on recruitment of blood volume as an alternative for increasing QECMO, based on the concepts of venous return.

Methods:
In a closed chest, centrally cannulated porcine preparation (n = 9) in ventricular fibrillation and VA-ECMO with vented left atrium, mean systemic filling pressure (MSFP), and venous return driving pressure (VRdP) were determined in Euvolemia, during Vasoconstriction (norepinephrine 0.05, 0.125, and 0.2 μg/kg/min) and after Volume Expansion (3 boluses of 10 mL/kg Ringer's lactate). Maximum achievable QECMO was examined.

Results:

Vasoconstriction and Volume Expansion both increased maximum achievable QECMO, delivery of oxygen (DO2), and MSFP, but right atrial pressure increased in parallel. VRdP did not change. The vascular elastance curve was shifted to the left by Vasoconstriction, with recruitment of stressed volume. It was shifted to the right by Volume Expansion with direct expansion of stressed volume. Volume Expansion decreased resistance to venous return and pump afterload.

Conclusions:
In a circulation completely dependent on ECMO support, maximum achievable flow directly depended on the vascular factors governing venous return—i.e., closing conditions, stressed vascular volume and the elastance and resistive properties of the vasculature. Both treatments increased maximum achievable ECMO flow at stable DO2, via increases in stressed volume by different mechanisms. Vascular resistance and pump afterload decreased with Volume Expansion.
The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies
Authors: Conde Virginia , Tomasevic Leo , Akopian Irina , Stanek Konrad , Saturnino Guilherme B. , Thielscher Axel , Bergmann Til Ole , Siebner Hartwig Roman 
Published: June 2018

AbstractTranscranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud “click” sound, the TMS-evoked EEG potential (TEP) not only reflects neural activity induced by transcranial neuronal excitation but also neural activity reflecting somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the study design to enable a dissociation between truly transcranial and non-transcranial components of TEPs.
High genetic diversity and presence of genetic structure characterise the Corso-Sardinian endemicsRuta corsicaandRuta lamarmorae(Rutaceae)
Authors: Meloni Marilena , Dettori Caterina Angela , Reid Andrea , Bacchetta Gianluigi , Hugot Laetitia , Conti Elena 
Published: June 2018

SummaryCorsica and Sardinia form one of the ten areas with highest biodiversity in the Mediterranean and are considered one of the priority regions for conservation in Europe. In order to preserve the high levels of endemism and biological diversity at different hierarchical levels, knowledge of the evolutionary history and current genetic structure of Corso-Sardinian endemics is instrumental. Microsatellite markers were newly developed and used to study the genetic structure and taxonomic status ofRuta corsicaandRuta lamarmorae, rare endemics of Corsica and Sardinia, respectively, and previously considered a single species. Our analyses identified high levels of genetic variation within each species (P=0.883,He=0.543 forR. corsica; P=0.972,He=0.627 forR. lamarmorae). Intrinsic traits of the species (hermaphroditism, proterandry and polyploidy) and island-dependent factors (i.e. age, origin and history of the islands) might explain the detected high levels of genetic variation. We discovered differentiation betweenR. corsicaandR. lamarmorae, and genetic structure within each species, which are consistent with the observation of low dispersal ability for both species. Our genetic results support the recent taxonomic classification ofR. corsicaandR. lamarmoraeas separate species and suggest that they diverge at only few loci. OneR. corsicapopulation (SA) strongly differed from all other studied populations and appeared to be the product of hybridization between the two species in STRUCTURE analyses. Our results provide important insights for the conservation of the two rare endemics. Further genetic analyses are recommended forR. lamarmoraeand for population SA (R. corsica).
Connectivity analyses of bioenergetic changes in schizophrenia: Identification of novel treatments
Authors: Sullivan Courtney R. , Mielnik Catharine A. , O’Donovan Sinead M. , Funk Adam J. , Bentea Eduard , DePasquale Erica A.K. , Wen Zhexing , Haroutunian Vahram , Katsel Pavel , Ramsey Amy J. , Meller Jarek , McCullumsmith Robert E. 
Published: June 2018

ABSTRACTWe utilized a cell-level approach to examine glycolytic pathways in the DLPFC of subjects with schizophrenia (n=16) and control (n=16) subjects and found decreased mRNA expression of glycolytic enzymes in pyramidal neurons, but not astrocytes. To replicate these novel bioenergetic findings, we probed independent datasets for bioenergetic targets and found similar abnormalities. Next, we used a novel strategy to build a schizophrenia bioenergetic profile by a tailored application of the Library of Integrated Network-Based Cellular Signatures data portal (iLINCS) and investigated connected cellular pathways, kinases, and transcription factors using Enrichr. Finally, with the goal of identifying drugs capable of “reversing” the bioenergetic schizophrenia signature, we performed a connectivity analysis with iLINCS and identified peroxisome proliferator-activated receptor (PPAR) agonists as promising therapeutic targets. We administered a PPAR agonist to the GluN1 knockdown model of schizophrenia and found it improved long-term memory. Taken together, our findings suggest that tailored bioinformatics approaches, coupled with the LINCS library of transcriptional signatures of chemical and genetic perturbagens may be employed to identify novel treatment strategies for schizophrenia and related diseases.
Faces and voices in the brain: a modality-general person-identity representation in superior temporal sulcus
Authors: Tsantani Maria , Kriegeskorte Nikolaus , McGettigan Carolyn , Garrido Lúcia 
Published: June 2018

AbstractFace-selective and voice-selective brain regions have been shown to represent face-identity and voice-identity, respectively. Here we investigated whether there are modality-general person-identity representations in the brain that can be driven by either a face or a voice, and that invariantly represent naturalistically varying face and voice tokens of the same identity. According to two distinct models, such representations could exist either in multimodal brain regions (Campanella and Belin, 2007) or in face-selective brain regions via direct coupling between face- and voice-selective regions (von Kriegstein et al., 2005). To test the predictions of these two models, we used fMRI to measure brain activity patterns elicited by the faces and voices of familiar people in multimodal, face-selective and voice-selective brain regions. We used representational similarity analysis (RSA) to compare the representational geometries of face- and voice-elicited person-identities, and to investigate the degree to which pattern discriminants for pairs of identities generalise from one modality to the other. We found no matching geometries for faces and voices in any brain regions. However, we showed crossmodal generalisation of the pattern discriminants in the multimodal right posterior superior temporal sulcus (rpSTS), suggesting a modality-general person-identity representation in this region. Importantly, the rpSTS showed invariant representations of face- and voice-identities, in that discriminants were trained and tested on independent face videos (different viewpoint, lighting, background) and voice recordings (different vocalizations). Our findings support the Multimodal Processing Model, which proposes that face and voice information is integrated in multimodal brain regions.Significance statementIt is possible to identify a familiar person either by looking at their face or by listening to their voice. Using fMRI and representational similarity analysis (RSA) we show that the right posterior superior sulcus (rpSTS), a multimodal brain region that responds to both faces and voices, contains representations that can distinguish between familiar people independently of whether we are looking at their face or listening to their voice. Crucially, these representations generalised across different particular face videos and voice recordings. Our findings suggest that identity information from visual and auditory processing systems is combined and integrated in the multimodal rpSTS region.
Structural insights on TRPV5 gating by endogenous modulators
Authors: Hughes Taylor E.T. , Pumroy Ruth A. , Yazici Aysenur Torun , Kasimova Marina A. , Fluck Edwin C. , Huynh Kevin W. , Samanta Amrita , Mulugu Sudheer , Zhou Z. Hong , Carnevale Vincenzo , Rohacs Tibor , Moiseenkova-Bell Vera Y. 
Published: June 2018

ABSTRACTTRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure revealed a novel binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure revealed two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery.
In a temporally segmented experience hippocampal neurons represent temporally drifting context but not discrete segments
Authors: Bladon J. H. , Sheehan D. J. , De Freitas C. S. , Howard M. W. 
Published: June 2018

AbstractThere is widespread agreement that episodic memory is organized into a timeline of past experiences. Recent work suggests that the hippocampus may parse the flow of experience into discrete episodes separated by event boundaries. A complementary body of work suggests that context changes gradually as experience unfolds. We recorded from hippocampal neurons as male long evans rats performed 6 blocks of an object discrimination task in sets of 15 trials. Each block was separated by removal from the testing chamber for a delay to enable segmentation. The reward contingency reversed from one block to the next to incentivize segmentation. We expected animals to hold two distinct, recurring representations of context to match the two distinct rule contingencies. Instead, we found that overtrained rats began each block neither above nor below chance but by guessing randomly. While many units had clear firing fields selective to the conjunction of objects in places, a significant population also reflected a continuously drifting code both within block and across blocks. Despite clear boundaries between blocks, we saw no neural evidence for event segmentation in this experiment. Rather, the hippocampal ensemble drifted continuously across time. This continuous drift in the neural representation was consistent with the lack of segmentation observed in behavior.Significance StatementThe neuroscience literature yet to reach consensus as to how hippocampal firing fields support the organizing of events across time in episodic memory. Initial reports of hippocampal activity focused on discrete episodes within which representations were stable, and across which representations remapped. However, it remains unclear whether this segmentation of representations is merely an artifact of cue responsivity. More recently, research has shown that a proportion of the population codes for temporal aspects of context by exhibiting varying degrees of drift in their firing fields. Drift is hypothesized to represent a continually evolving temporal context, however it is unclear whether this drift is continuous or is also a mere artifact of changing experiences. We recorded from the dorsal hippocampus of rats performing an object discrimination task that involved contexts that were segmented in time. Overtrained rats were unable to anticipate the identity of the upcoming context, but may have used context boundaries to their advantage. Event segmentation theory predicts that hippocampal ensembles would alternate between behaviorally-relevant segments. Contrary to these predictions, animals showed weak evidence of context segmentation, even across blocks with different reward contingencies. Hippocampal ensembles showed neither evidence of alternating between stable contexts nor sensitivity to context boundaries, but did show robust temporal drift.
Microtubule plus-tips act as signaling hubs for positioning the cleavage furrow during cytokinesis
Authors: Verma Vikash , Maresca Thomas J. 
Published: June 2018

ABSTRACTCell division in animal cells culminates with the formation of a contractile ring that divides the cytosol through formation of a cleavage furrow. Microtubules (MTs) are essential for furrow positioning, but the molecular nature of MT-derived spatial signals is unresolved. In this study essential cytokinesis regulators (the centralspindlin complex, aurora B kinase (ABK), and polo kinase) were visualized in Drosophila melanogaster (Dm) cells and found localize to and track MT plus-ends during cytokinesis. The RhoA GEF Pebble (Dm ECT2) did not robustly tip-track but became enriched at MT plus-tips rapidly following cortical contact resulting in RhoA activation and enrichment of myosin-regulatory light chain. Abrogation of cytokinesis regulator tip-tracking by EB1 depletion or deletion of a novel EB1-interaction motif (hxxPTxh) in the centralspindlin component RacGAP50C resulted in higher incidences of cytokinesis failure. We propose that EB1-dependent, MT plus-tip-based signaling hubs recruit cortical Dm ECT2 upon contact to locally activate RhoA.
Dynamics and spatial genomics of the nascent transcriptome in single mESCs by intron seqFISH
Authors: Shah Sheel , Takei Yodai , Zhou Wen , Lubeck Eric , Yun Jina , Koulena Noushin , Liaw Eric J. , Amin Mina , Cai Long 
Published: June 2018

SummaryRecent single cell experiments have revealed significant heterogeneities at the levels of transcription, DNA methylation and chromosome organization in individual cells. However, existing method of profiling mRNAs effectively averages transcriptional dynamics over many hours due to hours-long life time of most mRNAs. To capture the instantaneous activity of the transcriptome that reflects the rapid regulatory changes in cells, we imaged up to 10,421 nascent transcription active sites (TAS) in single mouse embryonic stem cells using seqFISH followed by multiple rounds of single molecule FISH and immunofluorescence. We observed that nascent transcription active sites appear to be distributed on the surface of individual chromosome territories and are dispersed throughout the nucleus. In addition, there are significant variability in the number of active transcription sites in single cells, representing globally more active to quiescent states. These states interconverted on the time scale of 2 hours as determined by a single cell pulse-chase experiment. Thus, transcriptome level seqFISH experiments provide an unprecedented spatial and dynamic view of chromosome organization and global nascent transcription activity in single cells.
Sampling native-like structures of RNA-protein complexes through Rosetta folding and docking
Authors: Kappel Kalli , Das Rhiju 
Published: June 2018

AbstractRNA-protein complexes underlie numerous cellular processes including translation, splicing, and posttranscriptional regulation of gene expression. The structures of these complexes are crucial to their functions but often elude high-resolution structure determination. Computational methods are needed that can integrate low-resolution data for RNA-protein complexes while modeling de novo the large conformational changes of RNA components upon complex formation. To address this challenge, we describe a Rosetta method called RNP-denovo to simultaneously fold and dock RNA to a protein surface. On a benchmark set of structurally diverse RNA-protein complexes that are not solvable with prior strategies, this fold-and-dock method consistently sampled native-like structures with better than nucleotide resolution. We revisited three past blind modeling challenges in which previous methods gave poor results: human telomerase, an RNA methyltransferase with a ribosomal RNA domain, and the spliceosome. When coupled with the same sparse FRET, cross-linking, and functional data used in previous work, RNP-denovo gave models with significantly improved accuracy. These results open a route to computationally modeling global folds of RNA-protein complexes from low-resolution data.
mTOR-dependent phosphorylation controls TFEB nuclear export
Authors: Napolitano Gennaro , Esposito Alessandra , Choi Heejun , Benedetti Valerio , Matarese Maria , Di Malta Chiara , Monfregola Jlenia , Medina Diego Luis , Lippincott-Schwartz Jennifer , Ballabio Andrea 
Published: June 2018

AbstractThe transcriptional activation of catabolic processes during starvation is induced by the nuclear translocation and consequent activation of transcription factor EB (TFEB), a master modulator of autophagy and lysosomal biogenesis. However, how TFEB is inactivated upon nutrient re-feeding is currently unknown. Here we show that TFEB subcellular localization is dynamically controlled by its continuous shuttling between the cytosol and the nucleus, with the nuclear export representing a limiting step. TFEB nuclear export is mediated by CRM1 and is modulated by nutrient availability via mTOR-dependent hierarchical multisite phosphorylation of serines S142 and S138, which are localized in proximity of a nuclear export signal (NES). Our data reveal that modulation of TFEB nuclear export via phosphorylation plays a major role in the modulation of TFEB localization and activity.
Enhanced synaptic properties of the prefrontal cortex and hippocampus after learning a spatial working memory task in adult male mice
Authors: Stavroulaki Vasiliki , Ioakeimidis Vasileios , Konstantoudaki Xanthippi , Sidiropoulou Kyriaki 
Published: June 2018

AbstractWorking memory (WM) is the ability to hold on-line and manipulate information. The prefrontal cortex (PFC) is a key brain region involved in WM, while the hippocampus is also involved, particularly, in spatial WM. Although several studies have investigated the neuronal substrates of WM in trained animals, the effects and the mechanisms underlying learning WM tasks have not been explored. In our study, we investigated the effects of learning WM tasks in mice on the function of PFC and hippocampus, by training mice in the delayed alternation task for 9 days (adaptive group). This group was compared to naïve mice that stayed in their homecage (naïve) and mice trained in the alternation procedure only (non-adaptive). Following training, a cohort of mice (Experiment A) was tested in the left-right discrimination task and the reversal learning task, while another cohort (Experiment B) was tested in the attention set- shifting task (AST). The adaptive group performed significantly better in the reversal learning task (Experiment A) and AST (Experiment B), compared to non-adaptive and naïve groups. At the end of the behavioral experiments in Experiment A, field excitatory post-synaptic potential (fEPSP) recordings were performed in PFC and hippocampal brain slices. The adaptive group had enhanced the long-term potentiation (LTP) in the PFC, compared to the other groups. In the hippocampus, both the adaptive and the non-adaptive groups exhibited increased fEPSP compared to the naive group, but no differences in LTP. In Experiment B, the dendritic spine density was measured, which, in the PFC, was found increased in the adaptive group, compared to the non-adaptive and naive groups. In the hippocampus, there was an increase in mature dendritic spine density in the adaptive group, compared to the other two groups. Our results indicate a role for long-term potentiation and dendritic spine density in learning WM tasks.Significance statementWorking memory (WM) allows for transient storage and manipulation of information and has a central role in cognition. While a great number of research studies have investigated the mechanisms underlying the ‘memory’ part of WM in well-trained animals, the mechanisms that underlie learning WM tasks are not known. Studies have indicated that learning a WM tasks alters and enhances neuronal firing during the delay period, suggesting that long-term plasticity mechanisms could be involved. Our results in this study suggest that learning a working memory task primarily increases long-term potentiation and dendritic spine density in the prefrontal cortex, providing evidence for a role of long-term plasticity processes in learning working memory tasks. Furthermore, learning working memory tasks enhances cognitive flexibility.