bluuebunny/crossref_metadata_2025_split huggingface dataset:
New insights on the ventral attention network: Active suppression and involuntary recruitment during a bimodal task
Authors: Solís-Vivanco Rodolfo , Jensen Ole , Bonnefond Mathilde 
Published: September 2019

ABSTRACTReorienting attention to unexpected events is essential in daily life. fMRI studies have revealed the involvement of the ventral attention network (VAN), including the temporo-parietal junction (TPJ), in such process. In this MEG study with 34 participants (17 women) we used a bimodal (visual/auditory) attention task to determine the neuronal dynamics associated with suppression of the activity of the VAN during top-down attention and its recruitment when information from the unattended sensory modality is involuntarily integrated. We observed an anticipatory power increase of alpha/beta (12-20 Hz) oscillations in the VAN following a cue indicating the modality to attend. Stronger VAN power increases predicted better task performance, suggesting that the VAN suppression prevents shifting attention to distractors. Moreover, the TPJ was synchronized with the frontal eye field in that frequency band, suggesting that the dorsal attention network (DAN) might participate in such suppression. Furthermore, we found a 12-20 Hz power decrease, in both the VAN and DAN, when information of both sensory modalities was congruent, suggesting an involvement of these networks for attention capture. Our results show that effective multimodal attentional reorientation includes the modulation of the VAN and DAN through upper-alpha/beta oscillations. Altogether these results indicate that the suppressing role of alpha/beta oscillations might operate beyond sensory regions.SIGNIFICANCE STATEMENTReorienting attention to unexpected events from multiple sensory sources is essential in daily life. We explored the dynamics of the ventral attention network (VAN), a set of brain regions related to attentional reorienting, when relevant information was anticipated (i.e. during top-down attention) and when unexpected congruent information from another sensory modality was presented (involuntary attentional capture). We report that activity in the alpha/beta range (12-20 Hz) within the VAN indexed both top-down and attentional capture processes. Also, the VAN was synchronized with the dorsal attention network in this frequency band, suggesting an integrated role of both networks for attentional regulation. Our results shed light on the neurophysiological mechanisms that the brain carry out for reorienting attention to relevant environmental stimuli.
RNF144A shapes the hierarchy of cytokine signaling to provide protective immunity against influenza
Authors: Afzali B. , Kim S. , West E. , Nova-Lamperti E. , Cheru N. , Nagashima H. , Yan B. , Freiwald T , Merle N. , Chauss D. , Bijlmakers M. , Weitsman G. , Yu Z. , Jankovic D. , Mitra S. , Villarino A. , Kemper C. , Laurence A. , Kazemian M. , O’Shea J.J. , John S. 
Published: September 2019

AbstractCytokine-induced signaling pathways are tightly regulated and self-limiting, as their dysregulation causes immune disorders and cancer. The precise mechanisms that fine-tune these responses are incompletely understood. We show that the E3 ubiquitin ligaseRNF144Ais an IL-2/STAT5-induced gene in T cells and critically orchestrates the hierarchy of IL-2R signaling to promote STAT5 activation and limit RAF-ERK-MAPK output from the IL-2R. Mechanistically, RNF144A increased the interaction between IL-2Rβ and STAT5 and polyubiquitinated RAF1, enhancing its proteasomal degradation and preventing the formation of the potent RAF1/BRAF kinase complex. CD8+T cells fromRnf144a–/–mice had impaired IL-2-induction of effector genes, includingTnfand granzymes, and these mice demonstrated increased susceptibility to influenza. Reduced RNF144A expression was associated with more severe influenza in humans and its expression in patients was a biomarker distinguishing moderate from severe disease. These studies reveal a vital physiological role for RNF144A in maintaining the fidelity of IL-2R signaling in CTLs to prevent severe inflammation in response to infection.One Sentence SummaryRNF144A promotes anti-viral immunity by regulating the hierarchy of cytokine signal output
COPO: a metadata platform for brokering FAIR data in the life sciences
Authors: Etuk Anthony , Shaw Felix , Gonzalez-Beltran Alejandra , Johnson David , Laporte Marie-Angélique , Rocca-Serra Philippe , Arnaud Elizabeth , Devare Medha , Kersey Paul J , Sansone Susanna-Assunta , Davey Robert P 
Published: September 2019

AbstractScientific innovation is increasingly reliant on data and computational resources. Much of today’s life science research involves generating, processing, and reusing heterogeneous datasets that are growing exponentially in size. Demand for technical experts (data scientists and bioinformaticians) to process these data is at an all-time high, but these are not typically trained in good data management practices. That said, we have come a long way in the last decade, with funders, publishers, and researchers themselves making the case for open, interoperable data as a key component of an open science philosophy. In response, recognition of the FAIR Principles (that data should be Findable, Accessible, Interoperable and Reusable) has become commonplace. However, both technical and cultural challenges for the implementation of these principles still exist when storing, managing, analysing and disseminating both legacy and new data.COPO is a computational system that attempts to address some of these challenges by enabling scientists to describe their research objects (raw or processed data, publications, samples, images, etc.) using community-sanctioned metadata sets and vocabularies, and then use public or institutional repositories to share it with the wider scientific community. COPO encourages data generators to adhere to appropriate metadata standards when publishing research objects, using semantic terms to add meaning to them and specify relationships between them. This allows data consumers, be they people or machines, to find, aggregate, and analyse data which would otherwise be private or invisible. Building upon existing standards to push the state of the art in scientific data dissemination whilst minimising the burden of data publication and sharing.AvailabilityCOPO is entirely open source and freely available on GitHub athttps://github.com/collaborative-open-plant-omics. A public instance of the platform for use by the community, as well as more information, can be found atcopo-project.org.
LAX28 is required for assembly of the inner dynein arm l1 and tether/tether head complex in the Leishmania flagellum
Authors: Beneke Tom , Banecki Katherine , Fochler Sophia , Gluenz Eva 
Published: September 2019

AbstractMotile eukaryotic flagella beat through coordinated activity of dynein motor proteins yet the mechanisms of dynein coordination and regulation are incompletely understood. The inner dynein arm IDA f/I1 complex and the tether/tether head (T/TH) complex are thought to be key regulators but, unlike IDA f/I1, T/TH proteins show limited conservation across flagellates. Here we characterised T/TH-associated proteins in the protist Leishmania mexicana. Proteome analysis of ΔCFAP44 mutant axonemes showed that they lacked IDA f/I1 protein IC140 and a novel 28-kDA axonemal protein, LAX28. Sequence analysis identified similarities between LAX28 and the uncharacterised human sperm tail protein TEX47, sharing features with sensory BLUF-domain proteins. Leishmania lacking LAX28, CFAP44 or IC140 retained some motility albeit with reduced swimming speed and directionality and a propensity for flagellar curling. Expression of tagged proteins in different null mutant backgrounds showed that the axonemal localisation of LAX28 requires CFAP44 and IC140, and the axonemal localisations of CFAP44 and IC140 both depend on LAX28. These data demonstrate a role for LAX28 in motility and show mutual dependencies of IDA f/1I and T/TH-associated proteins for axonemal assembly in Leishmania.Summary StatementThe inner dynein arm f/l1 complex is required for coordinating flagellar motility. Here we show that LAX28 is needed for its function and localization in the flagellum of Leishmania mexicana.
Single-cell time-series mapping of cell fate trajectories reveals an expanded developmental potential for human PSC-derived distal lung progenitors
Authors: Hurley Killian , Ding Jun , Villacorta-Martin Carlos , Herriges Michael J. , Jacob Anjali , Vedaie Marall , Alysandratos Konstantinos D. , Sun Yuliang L. , Lin Chieh , Werder Rhiannon B. , Wilson Andrew A. , Mithal Aditya , Mostoslavsky Gustavo , Caballero Ignacio S. , Guttentag Susan H. , Ahangari Farida , Kaminski Naftali , Rodriguez-Fraticelli Alejo , Camargo Fernando , Bar-Joseph Ziv , Kotton Darrell N 
Published: September 2019

AbstractAlveolar epithelial type 2 cells (AEC2s) are the facultative progenitors responsible for maintaining lung alveoli throughout life, yet are difficult to access from patients for biomedical research or lung regeneration applications. Here we engineer AEC2s from human induced pluripotent stem cells (iPSCs) in vitro and use single cell RNA sequencing (scRNA-seq) to profile the detailed kinetics of their differentiation over time. We focus on both the desired target cells as well as those that appear to diverge to alternative endodermal fates. By combining scRNA-seq with lentiviral barcoding to trace differentiating clones, we reveal the bifurcating cell fate trajectories followed as primordial lung progenitors differentiate into mature AEC2s. We define the global transcriptomic signatures of primary developing human AEC2s from fetal through adult stages in order to identify the subset of in vitro differentiating cells that appear to recapitulate the path of in vivo development. In addition, we develop computational methods based on Continuous State Hidden Markov Models (CSHMM) to identify the precise timing and type of signals, such as over-exuberant Wnt responses, that induce some early multipotent NKX2-1+ progenitors to lose lung fate as they clonally diverge into a variety of non-lung endodermal lineages. Finally, we find that this initial developmental plasticity is regulatable via Wnt modulation, and subsides over time, ultimately resulting in iPSC-derived AEC2s that exhibit a stable phenotype and nearly limitless self-renewal capacity in vitro. Our methods and computational approaches can be widely applied to study and control directed differentiation, producing an inexhaustible supply of mature lineages, exemplified here by the generation of AEC2s.
Detection of anomalous high frequency events in human intracranial EEG
Authors: Charupanit Krit , Sen-Gupta Indranil , Lin Jack J , Lopour Beth A 
Published: September 2019

SummaryObjectiveHigh-frequency oscillations (HFOs) are a promising biomarker for the epileptogenic zone. However, no physiological definition of an HFO has been established, so detection relies on the empirical definition of an HFO derived from visual observation. This can bias estimates of HFO features such as amplitude and duration, thereby hindering their utility as biomarkers. Therefore, we set out to develop an algorithm that detects high frequency events in the intracranial EEG that stand out from the background and does not require assumptions about event amplitude or morphology.MethodWe propose the anomaly detection algorithm (ADA), which integrates several unsupervised machine learning techniques to identify segments of data that are distinct from the background. We apply ADA and a standard HFO detector using a root-mean-square amplitude threshold to intracranial EEG from 11 patients undergoing evaluation for epilepsy surgery. The rate, amplitude, and duration of the detected events and the percent overlap between the two detectors are compared.ResultIn the seizure onset zone (SOZ), ADA detected a subset of conventional HFOs. In non-SOZ channels, ADA detected at least twice as many events as the standard approach, including some conventional HFOs; however, ADA also identified many low and intermediate amplitude events missed by the standard amplitude-based method. The rate of ADA events was similar across all channels; however, the amplitude of ADA events was significantly higher in SOZ channels, and the threshold between SOZ and non-SOZ channels was relatively consistent across patients.SignificanceADA does not require human supervision, parameter optimization, or prior assumptions about event shape, amplitude, or duration. It provides an unbiased estimate of HFO features, and our results suggest that amplitude may differentiate SOZ and non-SOZ channels. Further studies will examine the utility of HFO amplitude as a biomarker for epilepsy surgical outcome.
Molecular Determinants of Substrate Selectivity of a Pneumococcal Rgg-regulated Peptidase-Containing ABC Transporter
Authors: Wang Charles Y , Medlin Jennifer S. , Nguyen Don R. , Disbennett W. Miguel , Dawid Suzanne 
Published: September 2019

AbstractPeptidase-containing ABC transporters (PCATs) are a widely distributed family of transporters which secrete double-glycine (GG) peptides. In the opportunistic pathogenStreptococcus pneumoniae(pneumococcus), the PCATs ComAB and BlpAB have been shown to secrete quorum-sensing pheromones and bacteriocins related to the competence and pneumocin pathways. Here, we describe another pneumococcal PCAT, RtgAB, encoded by thertglocus and found intact in 17% of strains. The Rgg/SHP-like quorum sensing system RtgR/S, which uses a peptide pheromone with a distinctive Trp-X-Trp motif, regulates expression of thertglocus and provides a competitive fitness advantage in a mouse model of nasopharyngeal colonization. RtgAB secretes a set of co-regulatedrtgGG peptides. ComAB and BlpAB, which share a substrate pool with each other, do not secrete thertgGG peptides. Similarly, RtgAB does not efficiently secrete ComAB/BlpAB substrates. We examined the molecular determinants of substrate selectivity between ComAB, BlpAB, and RtgAB and found that the GG peptide signal sequences contain all the information necessary to direct secretion through specific transporters. Secretion through ComAB and BlpAB depends largely on the identity of four conserved hydrophobic signal sequence residues previously implicated in substrate recognition by PCATs. In contrast, a motif situated at the N-terminal end of the signal sequence, found only inrtgGG peptides, directs secretion through RtgAB. These findings illustrate the complexity in predicting substrate-PCAT pairings by demonstrating specificity that is not dictated solely by signal sequence residues previously implicated in substrate recognition.ImportanceThe export of peptides from the cell is a fundamental process carried out by all bacteria. One method of bacterial peptide export relies on a family of transporters called peptidase-containing ABC transporters (PCATs). PCATs export so-called GG peptides which carry out diverse functions, including cell-to-cell communication and inter-bacterial competition. In this work, we describe a PCAT-encoding genetic locus,rtg, in the pathogenStreptococcus pneumoniae(pneumococcus). Thertglocus is linked to increased competitive fitness advantage in a mouse model of nasopharyngeal colonization. We also describe how thertgPCAT preferentially secretes a set of co-regulated GG peptides but not GG peptides secreted by other pneumococcal PCATs. These findings illuminate a relatively understudied part of PCAT biology: how these transporters discriminate between different subsets of GG peptides. Ultimately, expanding our knowledge of PCATs will advance our understanding of the many microbial processes dependent on these transporters.
A dynamic pattern of local auxin sources is required for root regeneration
Authors: Matosevich Rotem , Cohen Itay , Gil-Yarom Naama , Modrego Abelardo , Verna Carla , Scarpella Enrico , Efroni Idan 
Published: September 2019

AbstractFollowing removal of its stem cell niche, the root meristem can regenerate by recruitment of remnant cells from the stump. Regeneration is initiated by rapid accumulation of auxin near the injury site but the source of this auxin is unknown. Here, we show that auxin accumulation arises from the activity of multiple auxin biosynthetic sources that are newly specified near the cut site and that their continuous activity is required for the regeneration process. Auxin synthesis is highly localized and PIN-mediate transport is dispensable for auxin accumulation and tip regeneration. Roots lacking the activity of the regeneration competence factorERF115, or that are dissected at a zone of low-regeneration potential, fail to activate local auxin sources. Remarkably, restoring auxin supply is sufficient to confer regeneration capacity to these recalcitrant tissues. We suggest that regeneration competence relies on the ability to specify new local auxin sources in a precise spatio-temporal pattern.
Electrospun polyester-urethane scaffold preserves mechanical properties and exhibits strain stiffening during in situ tissue ingrowth and degradation
Authors: Krynauw Hugo , Omar Rodaina , Koehne Josepha , Limbert Georges , Davies Neil H , Bezuidenhout Deon , Franz Thomas 
Published: September 2019

AbstractConsistent mechanical performance from implantation through healing and scaffold degradation is highly desired for tissue-regenerative scaffolds, e.g. when used for vascular grafts. The aim of this study was the paired in vivo mechanical assessment of biostable and fast degrading electrospun polyester-urethane scaffolds to isolate the effects of material degradation and tissue formation after implantation. Biostable and degradable polyester-urethane scaffolds with substantial fibre alignment were manufactured by electrospinning. Scaffold samples were implanted paired in subcutaneous position in rats for 7, 14 and 28 days. Morphology, mechanical properties and tissue ingrowth of the scaffolds were assessed before implantation and after retrieval. Tissue ingrowth after 28 days was 83 ± 10% in the biostable scaffold and 77 ± 4% in the degradable scaffold. For the biostable scaffold, the elastic modulus at 12% strain increased significantly between 7 and 14 days and decreased significantly thereafter in fibre but not in cross-fibre direction. The degradable scaffold exhibited a significant increase in the elastic modulus at 12% strain from 7 to 14 days after which it did not decrease but remained at the same magnitude, both in fibre and in cross-fibre direction. Considering that the degradable scaffold loses its material strength predominantly during the first 14 days of hydrolytic degradation (as observed in our previous in vitro study), the consistency of the elastic modulus of the degradable scaffold after 14 days is an indication that the regenerated tissue construct retains it mechanical properties.
Immunization of mice with chimeric antigens displaying selected epitopes confers protection against intestinal colonization and renal damage caused by Shiga toxin-producingEscherichia coli
Authors: Montero David A. , Del Canto Felipe , Salazar Juan C. , Cespedes Sandra , Cádiz Leandro , Arenas-Salinas Mauricio , Reyes José , Oñate Ángel , Vidal Roberto M. 
Published: September 2019

AbstractShiga toxin-producingEscherichia coli(STEC) cause diarrhea and dysentery, which may progress to hemolytic uremic syndrome (HUS). Vaccination has been proposed as a preventive approach against STEC infection; however, there is no vaccine for humans and those used in animals reduce but do not eliminate the intestinal colonization of STEC. The OmpT, Cah and Hes proteins are widely distributed among clinical STEC strains and are recognized by serum IgG and IgA in patients with HUS. Here, we develop a vaccine formulation based on two chimeric antigens containing epitopes of OmpT, Cah and Hes proteins against STEC strains. Intramuscular and intranasal immunization of mice with these chimeric antigens elicited systemic and local long-lasting humoral responses. However, the class of antibodies generated was dependent on the adjuvant and the route of administration. Moreover, while intramuscular immunization with the combination of the chimeric antigens conferred protection against colonization by STEC O157:H7 and the intranasal conferred protection against renal damage caused by STEC O91:H21. This pre-clinical study supports the potential use of this formulation based on recombinant chimeric proteins as a preventive strategy against STEC infections.
Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity and functioning
Authors: He Liu , Kooistra Robbelien , Das Ravi , Oudejans Ellen , van Leen Eric V. , Ziegler Johannes , Portegies Sybren , de Haan Bart , van Regteren Altena Anna S. , Stucchi Riccardo , Altelaar Maarten A. F. , Wieser Stefan , Krieg Michael , Hoogenraad Casper C. , Harterink Martin 
Published: September 2019

SUMMARYNeurons are among the most highly polarized cell types. They possess structurally and functionally different processes, axon and dendrites, to mediate information flow through the nervous system. Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is little understood.Using the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubule-associated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cell cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals.
Neural processing of iterated prisoner’s dilemma outcomes indicates next-round choice and speed to reciprocate cooperation
Authors: Constantino Francisco Cervantes , Garat Santiago , Nicolaisen-Sobesky Eliana , Paz Valentina , Martínez-Montes Eduardo , Kessel Dominique , Cabana Álvaro , Gradin Victoria B 
Published: September 2019

AbstractElecting whether to cooperate with someone else is well typified in the iterated prisoner’s dilemma (iPD) game, although the neural processes that unfold after its distinct outcomes have been only partly described. Recent theoretical models emphasize the ubiquity of intuitive cooperation, raising questions on the neural timelines involved. We studied the outcome stage of an iPD with electroencephalography (EEG) methods. Results showed that neural signals that are modulated by the iPD outcomes can also be indicative of future choice, in an outcome-dependent manner: (i) after zero-gain ‘sucker’s payoffs’ (unreciprocated cooperation), a participant’s decision thereafter may be indicated by changes to the feedback-related negativity (FRN); (ii) after one-sided non-cooperation (participant gain), by the P3; (iii) after mutual cooperation, by late frontal delta-band modulations. Critically, faster choices to reciprocate cooperation were predicted, on a single-trial basis, by P3 and frontal delta modulations at the immediately preceding trial. Delta band signaling is considered in relation to homeostatic regulation processing in the literature. The findings relate feedback to decisional processes in the iPD, providing a first neural account of the brief timelines implied in heuristic modes of cooperation.