bluuebunny/crossref_metadata_2025 huggingface dataset:
Male parental investment reflects the level of partner contributions and brood value in tree swallows
Authors: Lendvai Ádám Z. , Akçay Çağlar , Stanback Mark , Haussmann Mark F. , Moore Ignacio T. , Bonier Frances
Published: November 2017

Biparental care presents an interesting case of cooperation and conflict between unrelated individuals. Several models have been proposed to explain how parents should respond to changes in each other’s parental care to maximize their own fitness, predicting no change, partial compensation, or matching effort as a response. Here, we present an experiment in tree swallows (Tachycineta bicolor) in which we increased the parental care of females by presenting them, but not their mates, with additional nestling begging calls using automated playbacks. We performed this experiment in two populations differing in future breeding opportunities and thus the intensity of conflict over current parental care. We found that in response to a temporary increase in female parental effort, males in the northern population with lower sexual conflict matched the increased effort, whereas males in the southern population did not. We also found that increases in parental care during playbacks were driven by the females (i.e., females initiated the increased effort and their mates followed them) in the northern population but not the southern population. These results support the idea that with incomplete information about the brood value and need, cues or signals from the partner might become important in coordinating parental care.
Biophysical models reveal the relative importance of transporter proteins and impermeant anions in chloride homeostasis
Authors: Düsterwald Kira M. , Currin Christopher B. , Burman Richard J. , Akerman Colin J. , Kay Alan R. , Raimondo Joseph V.
Published: November 2017

Fast synaptic inhibition in the nervous system depends on the transmembrane flux of Cl− ions based on the neuronal Cl− driving force. Established theories regarding the determinants of Cl− driving force have recently been questioned. Here we present biophysical models of Cl− homeostasis using the pump-leak model. Using numerical and novel analytic solutions, we demonstrate that the Na+/K+-ATPase, ion conductances, impermeant anions, electrodiffusion, water fluxes and cation-chloride cotransporters (CCCs) play roles in setting the Cl− driving force. Our models, together with experimental validation, show that while impermeant anions can contribute to setting [Cl−]i in neurons, they have a negligible effect on the driving force for Cl− locally and cell-wide. In contrast, we demonstrate that CCCs are well-suited for modulating Cl− driving force and hence inhibitory signalling in neurons. Our findings reconcile recent experimental findings and provide a framework for understanding the interplay of different chloride regulatory processes in neurons.
Ennet: construction of potential cancer-driving networks based on somatic enhancer mutations only
Authors: Cui Ya , Niu Yiwei , Teng Xueyi , Wang Dan , Luo Huaxia , Zhang Peng , Wu Wei , He Shunmin , Luo Jianjun , Chen Runsheng
Published: November 2017

Whole genome sequencing technology has facilitated the discovery of a large number of somatic mutations in enhancers (SMEs), whereas the utility of SMEs in tumorigenesis has not been fully explored. Here we present Ennet, a method to comprehensively investigate SMEs enriched networks (SME-networks) in cancer by integrating SMEs, enhancer-gene interactions and gene-gene interactions. Using Ennet, we performed a pan-cancer analysis in 2004 samples from 8 cancer types and found many well-known cancer drivers were involved in the SME-networks, includingESR1,SMAD3,MYC,EGFR,BCL2andPAX5. Meanwhile, Ennet also identified many new networks with less characterization but have potentially important roles in cancer, including a large SME-network in medulloblastoma (MB), which contains genes enriched in the glutamate receptor and neural development pathways. Interestingly, SME-networks are specific across cancer types, and the vast majority of the genes identified by Ennet have few mutations in gene bodies. Collectively, our work suggests that using enhancer-only somatic mutations can be an effective way to discover potential cancer-driving networks. Ennet provides a new perspective to explore new mechanisms for tumor progression from SMEs.
Deconstructing Procedural Memory: Different Learning Trajectories and Consolidation of Sequence and Statistical Learning
Authors: Simor Peter , Zavecz Zsofia , Horváth Kata , Éltető Noémi , Török Csenge , Pesthy Orsolya , Gombos Ferenc , Janacsek Karolina , Nemeth Dezso
Published: November 2017

Procedural learning is a fundamental cognitive function that facilitates efficient processing of and automatic responses to complex environmental stimuli. Here, we examined training-dependent and off-line changes of two sub-processes of procedural learning: namely, sequence learning and statistical learning. Whereas sequence learning requires the acquisition of order-based relationships between the elements of a sequence, statistical learning is based on the acquisition of probabilistic associations between elements. Seventy-eight healthy young adults (58 females and 20 males) completed the modified version of the Alternating Serial Reaction Time task that was designed to measure Sequence and Statistical Learning simultaneously. After training, participants were randomly assigned to one of three conditions: active wakefulness, quiet rest, or daytime sleep. We examined off-line changes in Sequence and Statistical Learning as well as further improvements after extended practice. Performance in Sequence Learning increased during training, while Statistical Learning plateaued relatively rapidly. After the off-line period, both the acquired sequence and statistical knowledge was preserved, irrespective of the vigilance state (awake, quiet rest or sleep). Sequence Learning further improved during extended practice, while Statistical Learning did not. Moreover, within the sleep group, cortical oscillations and sleep spindle parameters showed differential associations with Sequence and Statistical Learning. Our findings can contribute to a deeper understanding of the dynamic changes of multiple parallel learning and consolidation processes that occur during procedural memory formation.
Identifying Crohn’s disease signal from variome analysis
Authors: Wang Yanran , Astrakhan Yuri , Petersen Britt-Sabina , Schreiber Stefan , Franke Andre , Bromberg Yana
Published: November 2017

Background

After many years of concentrated research efforts, the exact cause of Crohn’s disease remains unknown. Its accurate diagnosis, however, helps in management and even preventing the onset of disease. Genome-wide association studies have identified 140 loci associated with CD, but these carry very small log odds ratios and are uninformative for diagnoses.

Results

Here we describe a machine learning method – AVA,Dx (Analysis of Variation for Association with Disease) – that uses whole exome sequencing data to make predictions of CD status. Using the person-specific variation in these genes from a panel of only 111 individuals, we built disease-prediction models informative of previously undiscovered disease genes. In this panel, our models differentiate CD patients from healthy controls with 71% precision and 73% recall at the default cutoff. By additionally accounting for batch effects, we are also able to predict individual CD status for previously unseen individuals from a separate CD study (84% precision, 73% recall).

Conclusions

Larger training panels and additional features, including regulatory variants and environmental factors, e.g. human-associated microbiota, are expected to improve model performance. However, current results already position AVA,Dx as both an effective method for highlighting pathogenesis pathways and as a simple Crohn’s disease risk analysis tool, which can improve clinical diagnostic time and accuracy.
Prefrontal D1 dopamine-receptor neurons and delta resonance in interval timing
Authors: Kim Young-Cho , Narayanan Nandakumar S.
Published: November 2017

Considerable evidence has shown that prefrontal neurons expressing D1-type dopamine receptors (D1DRs) are critical for working memory, flexibility, and timing. This line of work predicts that frontal neurons expressing D1DRs mediate cognitive processing. During timing tasks, one form this cognitive processing might take is time-dependent ramping activity — monotonic changes in firing rate over time. Thus, we hypothesized the prefrontal D1DR+ neurons would strongly exhibited time-dependent ramping during interval timing. We tested this idea using an interval-timing task in which we used optogenetics to tag D1DR+ neurons in the mouse medial frontal cortex (MFC). While 23% of MFC D1DR+ neurons exhibited ramping, this was significantly less than untagged MFC D1DR+ neurons. By contrast, MFC D1DR+ neurons had strong delta-frequency (1-4 Hz) coherence with other MFC ramping neurons. This coherence was phase-locked to cue onset and was strongest early in the interval. To test the significance of these interactions, we optogenetically stimulated MFC D1DR+ neurons early vs. late in the interval. We found that 2-Hz stimulation early in the interval was particularly effective in rescuing timing-related behavioral performance deficits in dopamine-depleted animals. These findings provide insight into MFC networks and have relevance for disorders such as Parkinson’s disease and schizophrenia.

Significance Statement

Prefrontal D1DRs are involved in cognitive processing and cognitive dysfunction in human diseases such as Parkinson’s disease and schizophrenia. We use optogenetics to identify these neurons, as well as neurons that are putatively connected to MFC D1DR+ neurons. We study these neurons in detail during an elementary cognitive task. These data could have relevance for cognitive deficits for Parkinson’s disease, schizophrenia, and other diseases involving frontal dopamine.
Knockdown of endogenous circulating C1 inhibitor induces neurovascular impairment, neuroinflammation and cognitive decline
Authors: Farfara Dorit , Feierman Emily , Richards Allison , Revenko Alexey S. , MacLeod Robert A. , Norris Erin H. , Strickland Sidney
Published: November 2017

Plasma proteins and activated immune cells are known contributors of vascular brain disorders. However, the mechanisms and routes involved are still unclear. In order to understand the cross-talk between plasma proteins and the brain, we knocked down circulating C1 inhibitor (C1INH) in wild-type (WT) mice using antisense-oligonucleotide (ASO) technique and examined the brain. C1INH is a plasma protein inhibitor of vascular inflammation induced by activation of the kallikrein-kinin system (KKS) and the complement system. This knockdown induced the activation of the KKS but spared the activation of the classical complement system. Activation of the KKS induced an upregulation of the bradykinin pathway in the periphery and the brain, resulting in hypotension. Blood-brain barrier (BBB) permeability, plasma protein extravasations, activated glial cells and elevated levels of IL-1beta, IL-6, TNF-alpha, and iNOS were detected in brains of C1INH ASO treated mice. Infiltrating innate immune cells were evident, entering the brain through the lateral ventricle walls and the neurovascular units. The mice showed normal motor functions, however, cognition was impaired. Altogether, our results highlight the important role of regulated plasma-C1INH as a gatekeeper of the neurovascular system. Thus, manipulation of C1INH in neurovascular disorders might be therapeutically beneficial.
A Model Mechanism Based Explanation of an In Vitro-In Vivo Disconnect for Improving Extrapolation and Translation
Authors: Smith Andrew K. , Xu Yanli , Ropella Glen E.P. , Hunt C. Anthony
Published: November 2017

An improved understanding of in vivo-to-in vitro hepatocyte changes is crucial to interpreting in vitro data correctly and further improving hepatocyte-based in vitro-to-in vivo extrapolations to human targets. We demonstrate using virtual experiments as a means to help untangle plausible causes of inaccurate extrapolations. We start with virtual mice that have biomimetic software livers. Earlier, using those mice, we discovered model mechanisms that enabled achieving quantitative validation targets while also providing plausible causal explanations for temporal characteristics of acetaminophen hepatotoxicity. We isolated virtual hepatocytes, created a virtual culture, and then conducted dose-response experiments in both culture and mice. We expected the two dose-response curves to be displaced. We were surprised that they crossed because it evidenced that simulated acetaminophen metabolism and toxicity are different for virtual culture and mouse contexts even though individual hepatocyte mechanisms were unchanged. Crossing dose-response curves is a virtual example of an in vivo-to-in vitro disconnect. We use detailed results of experiments to explain the disconnect. Individual hepatocytes contribute differently to system level phenomena. In liver, hepatocytes are exposed to acetaminophen sequentially. Relative production of the reactive acetaminophen metabolite is largest (smallest) in pericentral (periportal) hepatocytes. Because that sequential exposure is absent in culture, hepatocytes from different lobular locations do not respond the same. A virtual Culture-to-Mouse translation can stand as a scientifically challengeable theory explaining an in vitro-in vivo disconnect. It provides a framework to develop more reliable interpretations of in vitro observations, which then may be used to improve extrapolations.

Abbreviations

aHPC

analog hepatocyte

APAP

acetaminophen

CV

Central Vein

SS

sinusoidal segment

NAPQI

N-acetyl-p-benzoquinone imine

mitoD

mitochondrial damage products

nonMD

non-mitochondrial damage products
STIMULUS: Noninvasive Dynamic Patterns of Neurostimulation using Spatio-Temporal Interference
Authors: Cao Jiaming , Grover Pulkit
Published: November 2017

Using a systematic computational and modeling framework, we provide a novelSpatio-Temporal Interference-based stiMULation focUsing Strategy(STIMULUS) for high spatial precision noninvasive neurostimulation deep inside the brain. To do so, we first replicate the results of the recently proposed temporal interference (TI) stimulation (which was only tested in-vivo) in a computational model based on a Hodgkin-Huxley model for neurons and a model of current dispersion in the head. Using this computational model, we obtain a nontrivial extension of the 2-electrode-pair TI proposed originally to multielectrode TI (>2 electrode pairs) that yields significantly higher spatial precision. To further improve precision, we develop STIMULUS techniques for generating spatial interference patterns in conjunction with temporal interference, and demonstrate strict and significant improvements over multielectrode TI. Finally, we utilize the adaptivity that is inherent in STIMULUS to create multisite neurostimulation patterns that can be dynamically steered over time.
Module analysis captures pancancer genetically and epigenetically deregulated cancer driver genes for smoking and antiviral response
Authors: Champion Magali , Brennan Kevin , Croonenborghs Tom , Gentles Andrew J. , Pochet Nathalie , Gevaert Olivier
Published: November 2017

The availability of increasing volumes of multi-omics profiles across many cancers promises to improve our understanding of the regulatory mechanisms underlying cancer. The main challenge is to integrate these multiple levels of omics profiles and especially to analyze them across many cancers. Here we present AMARETTO, an algorithm that addresses both challenges in three steps. First, AMARETTO identifies potential cancer driver genes through integration of copy number, DNA methylation and gene expression data. Then AMARETTO connects these driver genes with co-expressed target genes that they control, defined as regulatory modules. Thirdly, we connect AMARETTO modules identified from different cancer sites into a pancancer network to identify cancer driver genes. Here we applied AMARETTO in a pancancer study comprising eleven cancer sites and confirmed that AMARETTO captures hallmarks of cancer. We also demonstrated that AMARETTO enables the identification of novel pancancer driver genes. In particular, our analysis led to the identification of pancancer driver genes of smoking-induced cancers and ‘antiviral’ interferon-modulated innate immune response.

Software availability

AMARETTO is available as an R package athttps://bitbucket.org/gevaertlab/pancanceramaretto

Highlights

We present an algorithm for pancancer identification of cancer driver genes based on multiomics data fusion

GPX2 is a novel driver gene in smoking induced cancers and validated using knockdown of GPX2 in the A549 cell line.

OAS2 is a novel driver gene defining cancers with an antiviral signature supported by increased infiltration of tumor-associated macrophages.

Research in context

We present an algorithm that combines multiple sources of molecular data to identify novel genes that are involved in cancer development. We applied this algorithm on multiple cancers in a combined fashion and identified a network of pancancer driver genes. We highlighted two genes in detail GPX2 and OAS2. We showed that GPX2 is an important cancer gene in smoking induced cancers, and validated our predictions using experimental data where GPX2 was inactivated in a lung cancer cell line. Similarly we showed that OAS2 is an important cancer driver gene in cancers that show an antiviral signature.
Cognitive Entities Underpinning Task Episodes
Authors: Farooqui Ausaf A , Manly Tom
Published: November 2017

Cognitive Entities Underpinning Task Episodes

Accounts of hierarchical cognition suggest that extended task episodes as one task entity and not individually execute their component acts. Such hierarchical execution is frequently thought to occur by first instantiating a sequence representation in working memory that then controls the identity and sequence of component steps. In contrast, we evidence hierarchical execution of extended behavior in situations where the identity and sequence of component steps was unknown and not linked to any sequence representation. Participants executed unpredictable trials wherein, depending on the margin color, they could either choose the smaller value or the font of the two numbers. Crucially, they were biased into construing a recurring instance of three or five trials as one task episode. Behavioral signs of hierarchy, identical to those seen previously with memorized sequence execution, were seen - High trial 1 RT, higher trial 1 RT before longer task episodes, and absence of trial level switch cost specifically across episode boundaries. This showed that hierarchical task sequence representations are not a requisite for hierarchical organization of cognition. Merely construing behavior to be executed as a task episode is enough for the accompanying cognition to be hierarchically organized. Task episodes are executed through the intermediation of episode related programs that are assembled at the beginning and control and organize cognition across time.
Generation of Mouse-Zebrafish Hematopoietic Tissue Chimeric Embryos for Hematopoiesis and Host-Pathogen Interaction Studies
Authors: Parada-Kusz Margarita , Clatworthy Anne , Hagedorn Elliott J. , Penaranda Cristina , Nair Anil V. , Henninger Jonathan E. , Ernst Christoph , Li Brian , Riquelme Raquel , Jijon Humberto , Villablanca Eduardo J. , Zon Leonard I. , Hung Deborah , Allende Miguel L.
Published: November 2017

Xenografts of the hematopoietic system are extremely useful as disease models and for translational research. Zebrafish xenografts have been widely used to monitor blood cancer cell dissemination and homing due to the optical clarity of embryos and larvae, which allow unrestrictedin vivovisualization of migratory events. To broaden the scope of xenotransplantation studies in zebrafish, we have developed a technique that transiently generates hematopoietic tissue chimeras by transplanting murine bone marrow cells into zebrafish blastulae. This procedure leads to mammalian cell integration into the fish developmental hematopoietic program. Monitoring zebrafish chimeras at different time points post fertilization usingin vivotime-lapse and confocal imaging showed murine cell co-localization with developing primitive and definitive hematopoietic tissues, intravasation into fish circulation, and dynamic hematopoietic cell-vascular endothelial and hematopoietic cell-niche interactions. Immunohistochemistry assays performed in chimeric animals showed that, after engraftment, murine cells expressed antigens related to i) hematopoietic stem and progenitor cells, ii) active cell proliferation, and iii) myeloid cell lineages. Lastly, xenografted zebrafish larvae infected withKlebsiella pneumoniaeshowed murine immune cells trafficking to bacterial foci and interacting with bacterial cells. Overall, these results show that mammalian bone marrow cells xenografted in zebrafish integrate into the host hematopoietic system revealing highly conserved molecular mechanisms of hematopoiesis between zebrafish and mammals. In addition, this procedure introduces a useful and simple method that improves and broadens the scope of hematopoietic tissue xenotransplantation studies in zebrafish.
A new sequencing-based women’s health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis
Authors: Bik Elisabeth M. , Bird Sara W. , Bustamante Juan P. , Leon Luis E. , Nieto Pamela A. , Addae Kwasi , Alegría-Mera Víctor , Bravo Cristian , Bravo Denisse , Cardenas Juan P. , Caughey Adam , Covarrubias Paulo C. , Pérez-Donoso José , Gass Graham , Gupta Sarah L. , Harman Kira , Hongo Donna Marie B. , Jiménez Juan C. , Kraal Laurens , Melis-Arcos Felipe , Morales Eduardo H. , Morton Amanda , Navas Camila F. , Nuñez Harold , Olivares Eduardo , Órdenes-Aenishanslins Nicolás , Ossandon Francisco J. , Phan Richard , Pino Raul , Soto-Liebe Katia , Varas Ignacio , Vera-Wolf Patricia , Walton Nathaniel A. , Almonacid Daniel E. , Goddard Audrey D. , Ugalde Juan A. , Richman Jessica , Apte Zachary S.
Published: November 2017

The composition of the vaginal microbiome, including both the presence of pathogens involved in sexually transmitted infections (STI) as well as commensal microbiota, has been shown to have important associations for a woman’s reproductive and general health. Currently, healthcare providers cannot offer comprehensive vaginal microbiome screening, but are limited to the detection of individual pathogens, such as high-risk human papillomavirus (hrHPV), the predominant cause of cervical cancer. There is no single test on the market that combines HPV, STI, and microbiome screening. Here, we describe a novel inclusive women’s health assay that combines self-sampling with sequencing-based HPV detection and genotyping, vaginal microbiome analysis, and STI-associated pathogen detection. The assay includes genotyping and detection of 14 hrHPV types, 5 low-risk HPV types (lrHPV), as well as the relative abundance of 32 bacterial taxa of clinical importance, includingLactobacillus,Sneathia,Gardnerella, and 4 pathogens involved in STI, with high sensitivity, specificity, and reproducibility. For each of these taxa, healthy ranges were determined in a group of 50 self-reported healthy women. The hrHPV portion of the test was evaluated against the Digene High-Risk HPV HC2 DNA test with vaginal samples obtained from 185 women. Results were concordant for 181/185 of the samples (overall agreement of 97.83%, Cohen’s kappa = 0.93), with sensitivity and specificity values of 94.74% and 98.64%, respectively. Two discrepancies were caused by the Digene assay’s known cross-reactivity with low-risk HPV types, while two additional samples were found to contain hrHPV not detected by Digene. This novel assay could be used to complement conventional cervical cancer screening, because its self-sampling format can expand access among women who would otherwise not participate, and because of its additional information about the composition of the vaginal microbiome and the presence of pathogens.
Biological Sequence Modeling with Convolutional Kernel Networks
Authors: Chen Dexiong , Jacob Laurent , Mairal Julien
Published: November 2017

The growing number of annotated biological sequences available makes it possible to learn genotype-phenotype relationships from data with increasingly high accuracy. When large quantities of labeled samples are available for training a model, convolutional neural networks can be used to predict the phenotype of unannotated sequences with good accuracy. Unfortunately, their performance with medium- or small-scale datasets is mitigated, which requires inventing new data-efficient approaches. In this paper, we introduce a hybrid approach between convolutional neural networks and kernel methods to model biological sequences. Our method enjoys the ability of convolutional neural networks to learn data representations that are adapted to a specific task, while the kernel point of view yields algorithms that perform significantly better when the amount of training data is small. We illustrate these advantages for transcription factor binding prediction and protein homology detection, and we demonstrate that our model is also simple to interpret, which is crucial for discovering predictive motifs in sequences. The source code is freely available athttps://gitlab.inria.fr/dchen/CKN-seq.
Stomach-brain synchrony binds neural representations of the body in a novel, delayed-connectivity resting-state network
Authors: Rebollo Ignacio , Devauchelle Anne-Dominique , Béranger Benoît , Tallon-Baudry Catherine
Published: November 2017

Resting-state networks offer a unique window into the brain’s functional architecture, but their characterization remains limited to instantaneous connectivity thus far. Here, we describe a novel resting-state network based on the delayed connectivity between the brain and the slow electrical rhythm (0.05 Hz) generated in the stomach. The gastric network cuts across classical resting-state networks with little overlap with autonomic regulation areas. This network is composed of regions with convergent functional properties involved in mapping bodily space through touch, action or vision, as well as mapping external space in bodily coordinates. The network is characterized by a precise temporal sequence of activations within a gastric cycle, beginning with somato-motor cortices and ending with the extrastriate body area and dorsal precuneus. Our results demonstrate that canonical resting-state networks based on instantaneous connectivity represent only one of the possible partitions of the brain into coherent networks based on temporal dynamics.
A Timer for analyzing temporally dynamic changes in transcription during differentiation in vivo
Authors: Bending David , Martín Paz Prieto , Paduraru Alina , Ducker Catherine , Marzaganov Erik , Laviron Marie , Kitano Satsuki , Miyachi Hitoshi , Crompton Tessa , Ono Masahiro
Published: November 2017

Understanding the mechanisms of cellular differentiation is challenging because differentiation is initiated by signaling pathways that drive temporally dynamic processes, which are difficult to analyse in vivo. We establish a new Tool, Timer-of-cell-kinetics-and-activity (Tocky [toki], time in Japanese). Tocky uses the Fluorescent Timer protein, which spontaneously shifts its emission spectrum from blue-to-red, in combination with computer algorithms to reveal the dynamics of differentiation in vivo. Using a transcriptional target of T cell receptor (TCR)-signaling, we establish Nr4a3-Tocky to follow downstream effects of TCR signaling. Nr4a3-Tocky reveals the temporal sequence of events during regulatory T cell (Treg) differentiation and shows that persistent TCR signals occur during Treg generation. Remarkably, antigen-specific T cells at the site of autoimmune inflammation also show persistent TCR signaling. In addition, by generating Foxp3-Tocky, we reveal the in vivo dynamics of demethylation of the Foxp3 gene. Thus, Tocky is a Tool for cell biologists to address previously inaccessible questions by directly revealing dynamic processes in vivo.

The authors establish a new Tool, Timer-of-cell-kinetics-and-activity (Tocky) revealing the temporal dynamics of cellular activation and differentiation in vivo. The tool analyses the temporal sequence of molecular processes during cellular differentiation and identifies cells that receive persistent signals in vivo.
Extra-field activity shifts the place field center of mass to encode aversion experience
Authors: Mamad Omar , Agayby Beshoy , Stumpp Lars , Reilly Richard B. , Tsanov Marian
Published: November 2017

The hippocampal place cells encode spatial representation but it remains unclear how they store concurrent positive or negative experiences. Here, we report on place field reconfiguration in response to an innately aversive odor trimethylthiazoline (TMT). The advantage of TMT is the absence of learning curve required for associative fear conditioning. Our study investigated if CA1 place cells, recorded from behaving rats, remap randomly or if their reconfiguration depends on the location of the aversive stimulus perception. Exposure to TMT increased the amplitude of hippocampal beta oscillations in two arms of a maze (TMT arms). We found that a population of place cells with fields located outside the TMT arms increased their activity (extra-field spiking) in the TMT arms during the aversive episodes. These cells exhibited significant shift of the center of mass towards the TMT arms in the subsequent post-TMT recording. The induction of extra-field plasticity was mediated by the basolateral amygdala complex (BLA). Photostimulation of the BLA triggered aversive behavior, synchronized response of hippocampal local field oscillations, augmented theta rhythm amplitude and increased the spiking of place cells for the first 100ms after the light delivery. This occurred only for the extra-field-but not for intra-field spikes. Optogenetic BLA-triggered an increase in extra-field spiking activity correlated to the degree of place field plasticity in the post-ChR2 recording session. Our findings demonstrate that the increased extra-field activity during aversive episodes mediates the degree of subsequent field plasticity.
Theta and alpha oscillations are traveling waves in the human neocortex
Authors: Zhang Honghui , Watrous Andrew J. , Patel Ansh , Jacobs Joshua
Published: November 2017

Human cognition requires the coordination of neural activity across widespread brain networks. Here we describe a new mechanism for large-scale coordination in the human brain: traveling waves of theta and alpha oscillations. Examining direct brain recordings from neurosurgical patients performing a memory task, we found contiguous clusters of cortex in individual patients with oscillations at specific frequencies between 2 to 15 Hz. These clusters displayed spatial phase gradients, indicating that the oscillations were traveling waves that propagated across the cortex at ∼0.25-0.75 m/s. Traveling waves were relevant behaviorally because their propagation correlated with task events and was more consistent when subjects performed the task well. Our findings suggest that traveling waves can be modeled by a network of coupled oscillators because the direction of wave propagation correlated with the spatial orientation of local frequency gradients. These findings suggest a role for traveling waves in supporting brain connectivity by organizing neural processes across space and time.
PPARD regulation in gastric progenitor cells drives gastric tumorigenesis in mice
Authors: Zuo Xiangsheng , Deguchi Yasunori , Xu Weiguo , Wei Daoyan , Tian Rui , Chen Weidong , Moussalli Micheline J. , Liu Yi , Mao Fei , Xu Min , Yang Yaying , Gao Shen , Jaoude Jonathan C. , Liu Fuyao , Gagea Mihai , Broaddus Russell , Xie Keping , Shureiqi Imad
Published: November 2017

Little is known about the cell origin of gastric cancer. Peroxisome proliferator-activated receptor-delta (PPARD) is a druggable ligand-activated nuclear receptor that impacts protumorigenic cellular events. However, PPARD’s role in tumorigenesis, especially gastric tumorigenesis, remains to be defined. We found that targeting PPARD overexpression in murine gastric progenitor cells (GPC), via a villin promoter, spontaneously induced gastric tumorigenesis that progressed to invasive adenocarcinoma. PPARD overexpression in GPC upregulated tumorigenic proinflammatory cytokine and CD44 expression, expanded GPC populationin vivo, enhanced GPC self-renewal and proliferation in organoid cultures, and endowed these cells with tumorigenic properties. Our findings identify PPARD as a driver of gastric tumorigenesis via GPC transformation.
Limitations of proposed signatures of Bayesian confidence
Authors: Adler William T. , Ma Wei Ji
Published: November 2017

The Bayesian model of confidence posits that confidence is the observer’s posterior probability that the decision is correct. It has been proposed that researchers can gain evidence in favor of the Bayesian model by deriving qualitative signatures of Bayesian confidence, i.e., patterns that one would expect to see if an observer was Bayesian, and looking for those signatures in human or animal data. We examine two proposed qualitative signatures, showing that their derivations contain hidden assumptions that limit their applicability, and that they are neither necessary nor sufficient conditions for Bayesian confidence. One signature is an average confidence of 0.75 for trials with neutral evidence. This signature only holds when class-conditioned stimulus distributions do not overlap and internal noise is very low. Another signature is that, as stimulus magnitude increases, confidence increases on correct trials but decreases on incorrect trials. This signature is also dependent on stimulus distribution type. There is an alternative form of this signature that has been applied in the literature; we find no indication that it is expected under Bayesian confidence, which resolves an ostensible discrepancy. We conclude that, to determine the nature of the computations underlying confidence reports, there may be no shortcut to quantitative model comparison.
The NSIGHT1 Randomized Controlled Trial: Rapid Whole Genome Sequencing for Accelerated Etiologic Diagnosis in Critically Ill Infants
Authors: Petrikin Josh E. , Cakici Julie A. , Clark Michelle M. , Willig Laurel K. , Sweeney Nathaly M. , Farrow Emily G. , Saunders Carol J. , Thiffault Isabelle , Miller Neil A. , Zellmer Lee , Herd Suzanne M. , Holmes Anne M. , Batalov Serge , Veeraraghavan Narayanana , Smith Laurie D. , Dimmock David P. , Leeder Steven J. , Kingsmore Stephen F.
Published: November 2017

Importance

Genetic disorders, including congenital anomalies, are a leading cause of morbidity and mortality in infants, especially in neonatal and pediatric intensive care units (NICU and PICU). While genomic sequencing is useful for diagnosis of genetic diseases, results are usually reported too late to guide inpatient management.

Objective

To test the hypothesis that rapid whole genome sequencing (rWGS) increases the proportion of infants in NICUs and PICUs receiving a genetic diagnosis within 28 days.

Design

An investigator-initiated, partially blinded, pragmatic, randomized controlled study with enrollment from October 2014 - June 2016, and follow up until December 2016.

Setting

A regional neonatal and pediatric intensive care unit in a tertiary referral childrens hospital.

Participants

Sixty five of 129 screened families with infants aged less than four months, in neonatal and pediatric intensive care units, and with illnesses of unknown etiology, completed the study.

Intervention

Parent and infant trio rWGS.

Main Outcome and Measure

The hypothesis and end-points were formulated a priori. The primary end-point was rate of genetic diagnosis within 28 days of enrollment or first standard test order.

Results

Twenty six female proband infants, 37 male infants, and two infants of undetermined sex were randomized to receive rWGS plus standard tests (n=32, cases) or standard tests alone (n=33, controls). The study was terminated early due to loss of equipoise: 63% (21) controls received genomic sequencing as standard tests. Nevertheless, intention to treat analysis showed the rate of genetic diagnosis within 28 days to be higher in cases (31%, ten of 32) than controls (3%, one of 33; difference, 28% [95% CI, 10% to 46%]; p=0.003). Among infants enrolled in the first 25 days of life, the rate of neonatal diagnosis was higher in cases (32%, seven of 22) than controls (0%, zero of 23; difference, 32% [95% CI, 11% to 53%]; p=0.004). Age at diagnosis (median in cases 25 days, range 14-90 days vs median in controls 130 days, range 37-451) and time to diagnosis (median in cases thirteen days, range 1-84 days vs median in controls 107 days, range 21-429 days) were significantly less in cases than controls (p=0.04).

CONCLUSIONS

rWGS increased the proportion of infants in a regional NICU and PICU who received a timely diagnosis of a genetic disease. Additional, adequately powered studies are needed to determine whether accelerated diagnosis is associated with improved outcomes in this setting. ClinicalTrials.gov Identifier: NCT02225522.
Fusicatenibacter Is Associated with Kefir Drinking
Authors: Sprague Richard
Published: November 2017

Daily 16s rRNA-based microbiome sampling reveals that consumption of the fermented drink, kefir, is associated with a previously-unexplored genus Fusicatenibacter of the Firmicutes phylum within family Lachnospiraceae.
CHRAC/ACF Contribute to the Repressive Ground State of Chromatin
Authors: Scacchetti Alessandro , Brueckner Laura , Jain Dhawal , Schauer Tamas , Zhang Xu , Schnorrer Frank , van Steensel Bas , Straub Tobias , Becker Peter B.
Published: November 2017

The chromatin remodeling complexes CHRAC and ACF combine the ATPase ISWI with the signature subunit ACF1. These enzymes catalyze well-studied nucleosome sliding reactions in vitro, but how their actions affect physiological gene expression is unclear. Here we explored the influence of Drosophila CHRAC/ACF on transcription by complementary gain- and loss-of-function approaches.

Targeting ACF1 to multiple reporter genes inserted at many different genomic locations revealed a context-dependent inactivation of poorly transcribed reporters in repressive chromatin. Accordingly, single-embryo transcriptome analysis of a Acf knock-out allele showed that only lowly expressed genes are de-repressed in the absence of ACF1. Finally, the nucleosome arrays in Acf-deficient chromatin show loss of physiological regularity, particularly in transcriptionally inactive domains.

Taken together our results highlight that ACF1-containing remodeling factors contribute to the establishment of an inactive ground state of the genome through chromatin organization.
Explanation implies causation?
Authors: Myint Leslie , Leek Jeffrey T. , Jager Leah R.
Published: November 2017

Most researchers do not deliberately claim causal results in an observational study. But do we lead our readers to draw a causal conclusion unintentionally by explaining why significant correlations and relationships may exist? Here we perform a randomized study in a data analysis massive online open course to test the hypothesis that explaining an analysis will lead readers to interpret an inferential analysis as causal. We show that adding an explanation to the description of an inferential analysis leads to a 15.2% increase in readers interpreting the analysis as causal (95% CI 12.8% - 17.5%). We then replicate this finding in a second large scale massive online open course. Nearly every scientific study, regardless of the study design, includes explanation for observed effects. Our results suggest that these explanations may be misleading to the audience of these data analyses.
The study of antibody responses to influenza neuraminidase using a lentiviral pseudotype based ELLA
Authors: Biuso Fabrizio , Carnell George , Montomoli Emanuele , Temperton Nigel
Published: November 2017

Influenza pseudotypes represent an alternative to wild type virus for serological assays. To date, pseudotypes (PV) have predominantly been used as surrogates for wild type viruses in microneutralisation assays, where the surface glycoprotein of interest and a reporter gene (such as Luciferase) are used to assess if virus entry into target cells could be inhibited by serum antibodies. The influenza neuraminidase (NA) has the ability to bud and release new virions with or without the contribution of Haemagglutinin (HA). Influenza pseudotypes expressing NA alone, or with HA, were produced to evaluate the antibody response against NA using the enzyme-linked lectin assay (ELLA). The expression of an avian HA with human NAs has enabled the detection of specific antibody reponses against the human circulating subtypes of NA. Within this study a PV-based ELLA assay has been investigated with a pilot panel of sera prepared for an international CONSISE study. Preliminary results have confirmed that the assay is sensitive and could potentially represent a valid alternative to the classical ELLA assay, which requires the employment of reassortant viruses.
Effect of phenol red dye on monocrystal growth, crystalline perfection, and optical and dielectric properties of zinc (tris) thiourea sulfate
Authors: Shkir Mohd. , Ganesh V. , AlFaify S. , Maurya K. K. , Vijayan N.
Published: November 2017

In this work, the growth of large size (∼25 × 29 × 5 mm and ∼25 × 24 × 6 mm) colorful single crystals of zinc (tris) thiourea sulfate (ZTS) in the presence of 0.05–2 wt% phenol red (PR) dye was achieved using a simple and low-cost technique. Powder X-ray diffraction patterns confirm the presence of PR dye, which is indicated by an enhancement of the Raman peak intensities, a shift in their position and the appearance of a few extra peaks. The quality of the grown crystals was assessed by high-resolution X-ray diffraction, which shows that the crystalline perfection of 1 wt% PR-dyed ZTS crystals is better than that of 2 wt% PR-dyed crystals. The measured UV–vis absorbance spectra show two additional, strong absorption bands at ∼430 and 558 nm in the dyed crystals, due to the presence of PR dye, along with a band at ∼276 nm which is present for all crystals but is slightly shifted for the dyed crystals. Photoluminescence spectra were recorded at two excitation wavelengths (λexc = 310 and 385 nm). The luminescence intensity is found to be enriched in dyed crystals, with some extra emission bands. An enhancement in the value of the dielectric constant and a.c. electrical conductivity was also observed in the dyed ZTS crystals.
Spherical harmonics analysis based on the Reuss model in elastic macro strain and stress determination by powder diffraction
Authors: Popa Nicolae C.
Published: November 2017

In this paper a new approach to macro strain/stress analysis by generalized spherical harmonics is presented. It consists of expanding the stress tensor weighted by texture in a series of generalized spherical harmonics with the ground state of expansion specific to the classical Reuss model of an isotropic polycrystal. Like previously reported models having a ground state of hydrostatic type [Popa & Balzar (2001). J Appl Cryst. 34, 187–195] and of Voigt type [Popa et al. (2014). J Appl Cryst.
34, 154–159], the actual model is appropriate for use with Rietveld refinement.
A combined characterization of clusters in naturally aged Al–Cu–(Li, Mg) alloys using small-angle neutron and X-ray scattering and atom probe tomography
Authors: Ivanov R. , Deschamps A. , De Geuser F.
Published: November 2017

A new methodology for the characterization of solute clusters leading to compositional fluctuations is presented and discussed. The methodology makes use of contrast variation arising from a combination of small-angle scattering using neutrons and X-rays, and adapts a model for solute correlation to extract the chemistry and length scale of clustered states after quench and after natural ageing. In three subsets of the Al–Cu system, Cu-rich clusters are reported for all cases. The presence of Mg strongly enhances Cu clustering in the naturally aged state and results in more than double the number of clusters in the complex Al–Cu–Li–Mg system. The results are compared with those obtained using atom probe tomography.
CarbonXS GUI: a graphical front-end for CarbonXS
Authors: Tsui Lok-kun , Garzon Fernando
Published: November 2017

The crystallographic structure of disordered carbons impacts their performance in components for fuel cells, batteries and catalyst supports. Obtaining parameters such as lattice constants and crystal domain size requires an appropriate model for these carbons, a task accomplished with the Fortran program CarbonXS published in 1993. CarbonXS GUI contains an updated version of CarbonXS and a graphical user interface wrapper. This new version provides a graphical method of configuring and operating CarbonXS, a calculation mode to simulate diffraction patterns, and immediate feedback in the form of fit–source and difference plots. CarbonXS GUI is available for free on Windows, Linux and Mac OSX at http://github.com/lktsui/carbon_xs_gui.
Building inorganic supramolecular architectures using principles adopted from the organic solid state
Authors: Đaković Marijana , Soldin Željka , Kukovec Boris-Marko , Kodrin Ivan , Aakeröy Christer B. , Baus Nea , Rinkovec Tamara
Published: November 2017

In order to develop transferable and practical avenues for the assembly of coordination complexes into architectures with specific dimensionality, a strategy utilizing ligands capable of simultaneous metal coordination and self-complementary hydrogen bonding is presented. The three ligands used, 2(1H)-pyrazinone, 4(3H)-pyrimidinone and 4(3H)-quinazolinone, consistently deliver the required synthetic vectors in a series of CdII coordination polymers, allowing for reproducible supramolecular synthesis that is insensitive to the different steric and geometric demands from potentially disruptive counterions. In all nine crystallographically characterized compounds presented here, directional intermolecular N—H...O hydrogen bonds between ligands on adjacent complex building blocks drive the assembly and orientation of discrete building blocks into largely predictable topologies. Furthermore, whether the solids are prepared from solution or through liquid-assisted grinding, the structural outcome is the same, thus emphasizing the robustness of the synthetic protocol. The details of the molecular recognition events that take place in this series of compounds have been clearly delineated and rationalized in the context of calculated molecular electrostatic potential surfaces.