bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous theta burst TMS of area MT+ impairs attentive motion tracking
Authors: Chakraborty Arijit , Tran Tiffany T. , Silva Andrew E. , Giaschi Deborah , Thompson Benjamin 
Published: April 2019

AbstractAttentive motion tracking deficits, measured using multiple object tracking (MOT) tasks, have been identified in a number of visual and neurodevelopmental disorders such as amblyopia and autism. These deficits are often attributed to the abnormal development of high-level attentional networks. However, neuroimaging evidence from amblyopia suggests that reduced MOT performance can be explained by impaired function in motion sensitive area MT+ alone. To test the hypothesis that MT+ plays an important role in MOT, we assessed whether modulation of MT+ activity using continuous theta burst stimulation (cTBS) influenced MOT performance in participants with normal vision. An additional experiment involving numerosity judgements of MOT stimulus elements was conducted to control for non-specific effects of MT+ cTBS on psychophysical task performance. The MOT stimulus consisted of 4 target and 4 distractor dots and was presented at 10° eccentricity in the right or left hemifield. Functional MRI-guided cTBS was applied to left MT+. Participants (n = 13, age:27 ± 3) attended separate active and sham cTBS sessions where the MOT task was completed before, 5 mins post and 30 mins post cTBS. Active cTBS significantly impaired MOT task accuracy relative to baseline for the right (stimulated) hemifield 5 mins (10 ± 2% reduction; t12= 1.95, p = 0.03) and 30 mins (14 ± 3% reduction; t12= 2.96, p = 0.01) post stimulation. No impairment occurred within the left (control) hemifield after active cTBS or for either hemifield after sham cTBS. Numerosity task performance was unaffected by cTBS. These results highlight the importance of lower-level motion processing for MOT and suggest that abnormal function of MT+ alone is sufficient to cause a deficit in MOT task performance.
Chromatin-lamin B1 interaction promotes genomic compartmentalization and constrains chromatin dynamics
Authors: Chang Lei , Li Mengfan , Shao Shipeng , Xue Boxin , Hou Yingping , Zhang Yiwen , Li Ruifeng , Li Cheng , Sun Yujie 
Published: April 2019

AbstractThe eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized chromatin architecture and dynamics remains poorly understood. Here by combining imaging and Hi-C sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to chromatin redistribution and decompaction. Consequently, the inter-chromosomal interactions and overlap between chromosome territories are increased. Moreover, Hi-C data revealed that lamin B1 is required for the integrity and segregation of chromatin compartments but not for the topologically associating domains (TADs). We further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nuclear interior. Taken together, our data suggest that chromatin-lamin B1 interactions promote chromosomal territory segregation and genomic compartmentalization, and confine chromatin dynamics, supporting its crucial role in chromatin higher-order structure and dynamics.
Native molecule sequencing by nano-ID reveals synthesis and stability of RNA isoforms
Authors: Maier Kerstin C. , Gressel Saskia , Cramer Patrick , Schwalb Björn 
Published: April 2019

AbstractEukaryotic genes often generate a variety of RNA isoforms that can lead to functionally distinct protein variants. The synthesis and stability of RNA isoforms is however poorly characterized. The reason for this is that current methods to quantify RNA metabolism use ‘short-read’ sequencing that cannot detect RNA isoforms. Here we present nanopore sequencing-based Isoform Dynamics (nano-ID), a method that detects newly synthesized RNA isoforms and monitors isoform metabolism. nano-ID combines metabolic RNA labeling, ‘long-read’ nanopore sequencing of native RNA molecules and machine learning. Application of nano-ID to the heat shock response in human cells reveals that many RNA isoforms change their synthesis rate, stability, and splicing pattern. nano-ID also shows that the metabolism of individual RNA isoforms differs strongly from that estimated for the combined RNA signal at a specific gene locus. And although combined RNA stability correlates with poly(A)-tail length, individual RNA isoforms can deviate significantly. nano-ID enables studies of RNA metabolism on the level of single RNA molecules and isoforms in different cell states and conditions.
Spectral tilt underlies mathematical problem solving
Authors: Randazzo Michael J. , Ezzyat Youssef , Kahana Michael J. 
Published: April 2019

AbstractNeural activity associated with successful cognition appears as a tilt in the power spectrum of the local field potential, wherein increases in high-frequency power accompany decreases in low frequency power. Whereas this pattern has been shown in a wide range of memory tasks, it is unknown whether this increased spectral tilt reflects underlying memory-specific processes or rather a domain-general index of task engagement. To address the question of whether increased spectral tilt reflects increased attention to a cognitive task, we collected intracranial recordings from three hundred thirty neurosurgical patients as they performed a mathematical problem solving task. We used a mathematical problem solving task, because it allowed us to decouple task-specific processes with domain-general attention in a novel way. Using a statistical model to control for inherent problem complexity, we classified individual math problems based on whether a subject performed faster than predicted (high-attention orfast) or slower than predicted (low-attention, orslow) based on residual response times. In contrast to the domain-general attentional account, problems that took longer than predicted produced stronger evidence for the spectral tilt: widespread increases in high frequency (31–180 Hz) power and decreases in low frequency (3–17 Hz) power across frontal, temporal, and parietal cortices. The pattern emerged early within each trial and was sustained throughout the response period but was not observed in the medial temporal lobe. The data show that engaging in mathematical problem solving leads to a distributed spectral tilt pattern, even when accounting for variability in performance driven by the arithmetic demands of the problems themselves, and suggest that broadband changes in the power spectrum reflect an index of information processing in the brain beyond simple attention to the cognitive task.
Megaplasmids on the Rise: Combining Sequencing Approaches to Fully Resolve a Carbapenemase-Encoding Plasmid in a Proposed NovelPseudomonasSpecies
Authors: Botelho João , Lood Cédric , Partridge Sally R. , van Noort Vera , Lavigne Rob , Grosso Filipa , Peixe Luísa 
Published: April 2019

AbstractHorizontal transfer of plasmids plays a pivotal role in the dissemination of antibiotic resistance genes and emergence of multidrug-resistant bacteria. Sequencing of plasmids is thus paramount for the success of accurate epidemiological tracking strategies in the hospital setting and routine surveillance. Here, we combine Nanopore and Illumina sequencing to fully assemble a carbapenemase-encoding megaplasmid carried by a clinical isolate belonging to a putative novelPseudomonasspecies. FFUP_PS_41 has a multidrug resistance phenotype and was initially identified asPseudomonas putida, but an average nucleotide identity below the cut-off for species delineation suggests a new species related to theP. putidaphylogenetic group. FFUP_PS_41 harbors a 498,516-bp untypable megaplasmid (pJBCL41) with low similarity compared with publicly available plasmids. pJBCL41 contains a full set of genes for self-transmission and genes predicted to be responsible for plasmid replication, partitioning, maintenance and heavy metal resistance. pJBCL41 carries a class 1 integron with the |aacA7|blaVIM-2|aacA4| cassette array (In103) located within a defective Tn402-like transposon that forms part of a 50,273-bp mosaic region bound by 38-bp inverted repeats typical of the Tn3family and flanked by 5-bp direct repeats. This region is composed of different elements, including additional transposon fragments, five insertion sequences and a Tn3-Derived Inverted-Repeat Miniature Element. The hybrid Nanopore/Illumina approach resulted in contiguous assemblies and allowed us to fully resolve a carbapenemase-encoding megaplasmid fromPseudomonasspp. The identification of novel megaplasmids will shed a new light on the evolutionary effects of gene transfer and the selective forces driving AR.
Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes
Authors: Katsuda Takeshi , Matsuzaki Juntaro , Yamaguchi Tomoko , Yamada Yasuhiro , Hosaka Kazunori , Takeuchi Atsuko , Saito Yoshimasa , Ochiya Takahiro 
Published: April 2019

AbstractHepatocytes are regarded as the only effective cell source for cell transplantation to treat liver diseases; however, their availability is limited due to a donor shortage. Thus, a novel cell source must be developed. We recently reported that mature rodent hepatocytes can be reprogrammed into progenitor-like cells with a repopulative capacity using small molecule inhibitors. Here, we demonstrate that hepatic progenitor cells can be obtained from human infant hepatocytes using the same strategy. These cells, named human chemically induced liver progenitors (hCLiPs), had a significant repopulative capacity in injured mouse livers following transplantation. hCLiPs redifferentiated into mature hepatocytes in vitro upon treatment with hepatic maturation-inducing factors. These redifferentiated cells exhibited cytochrome P450 (CYP) enzymatic activities in response to CYP-inducing molecules and these activities were comparable with those in primary human hepatocytes. These findings will facilitate liver cell transplantation therapy and drug discovery studies.
PBS3 and EPS1 complete salicylic acid biosynthesis from isochorismate in Arabidopsis
Authors: Torrens-Spence Michael P. , Bobokalonova Anastassia , Carballo Valentina , Glinkerman Christopher M. , Pluskal Tomáš , Shen Amber , Weng Jing-Ke 
Published: April 2019

AbstractSalicylic acid (SA) is an important phytohormone mediating both local and systemic defense responses in plants. Despite over half a century of research, how plants biosynthesize SA remains unresolved. In Arabidopsis, a major part of SA is derived from isochorismate, a key intermediate produced by the isochorismate synthase (ICS), which is reminiscent of SA biosynthesis in bacteria. Whereas bacteria employ an isochorismate pyruvate lyase (IPL) that catalyzes the turnover of isochorismate to pyruvate and SA, plants do not contain an IPL ortholog and generate SA from isochorismate through an unknown mechanism. Combining genetic and biochemical approaches, we delineated the SA biosynthetic pathway downstream of isochorismate in Arabidopsis. We show that PBS3, a GH3 acyl adenylase-family enzyme important for SA accumulation, catalyzes ATP- and Mg2+-dependent conjugation of L-glutamate primarily to the 8-carboxyl of isochorismate and yields the key SA biosynthetic intermediate isochorismoyl-glutamate A. Moreover, EPS1, a BAHD acyltransferase-family protein with previously implicated role in SA accumulation upon pathogen attack, harbors a noncanonical active site and an unprecedented isochorismoyl-glutamate A pyruvoyl-glutamate lyase (IPGL) activity that produces SA from the isochorismoyl-glutamate A substrate. Together, PBS3 and EPS1 form a two-step metabolic pathway to produce SA from isochorismate in Arabidopsis, which is distinct from how SA is biosynthesized in bacteria. This study closes a major knowledge gap in plant SA metabolism and would help develop new strategies for engineering disease resistance in crop plants.
Odor-background segregation of unknown odorants based on stimulus onset asynchrony in honey bees
Authors: Sehdev Aarti , Szyszka Paul 
Published: April 2019

ABSTRACTAnimals use olfaction to search for distant objects. Unlike vision, where objects are spaced out, olfactory information mixes when it reaches olfactory organs. Therefore, efficient olfactory search requires segregating odors that are mixed with background odors. Animals can segregate known target odors by detecting short differences in the arrival of odorants from different sources (stimulus onset asynchrony). However, it is unclear whether animals can also use stimulus onset asynchrony to segregate previously unknown odorants that have no innate or learned relevance. Using behavioral experiments in honey bees, we here show that stimulus onset asynchrony also improves odor-background segregation of unknown odorants. The stimulus onset asynchrony necessary to behaviorally segregate unknown odorants is in the range of seconds, which is two orders of magnitude larger than the previously reported stimulus asynchrony sufficient for segregating known odorants. We propose that for unknown odorants, odor-background segregation requires sensory adaptation to the background stimulus.
A Network Architecture for Bidirectional Neurovascular Coupling in Rat Whisker Barrel Cortex
Authors: Kumar Bhadra S. , Khot Aditi , Chakravarthy Srinivasa V , Pushpavanam S 
Published: April 2019

AbstractThe neurovascular coupling is mostly considered as a master-slave relationship between the neurons and the cerebral vessels: the neurons demand energy which the vessels supply in the form of glucose and oxygen. In the recent past both theoretical and experimental studies have suggested that the neurovascular coupling is a bidirectional system, a loop that includes a feedback signal from the vessels influencing neural firing and plasticity. An integrated model of bidirectionally connected neural network and vascular network is hence required to understand the relationship between the informational and metabolic aspects of neural dynamics. In this study, we present a computational model of the bidirectional neurovascular system in the whisker barrel cortex and study the effect of such coupling on neural activity and plasticity as manifest in the map formation. In this model, a biologically plausible self-organizing network model of rate coded, dynamic neurons is nourished by a network of vessels modeled using the biophysical properties of blood vessels. The neural layer which is designed to simulate the whisker barrel cortex of rat transmits the vasodilatory signals to the vessels. The feedback from the vessels is in the form of available oxygen for oxidative metabolism whose end result is the ATP necessary to fuel neural firing. The model captures the effect of the feedback from the vascular network on the neuronal map formation in the whisker barrel model under normal and pathological (Hypoxia and Hypoxia-Ischemia) conditions.Author SummaryAlthough neurovascular coupling is typically depicted as a unidirectional influence originating from the neurons and acting on the cerebral vessels, in reality it forms a bidirectional system, consisting of neuronal energy demand signals transmitted to the vessels, and a feedback of metabolic substrates from the vessels, that influence the neural firing and plasticity. We present a computational model of the bidirectional neurovascular coupling in the whisker barrel cortex of rats and study the effect of such coupling on neural activity and plasticity as manifest in the map formation. The model consists of a biologically plausible self-organizing dynamic, neural network model and a biophysical vascular network model that nourishes the neural network in the form of oxygen necessary for neural oxidative metabolism. The model reproduces the spatio-temporal hemodynamic responses observed in rat whisker barrel cortex. It also demonstrates the essentiality of the vascular feedback on the whisker barrel map formation under normal and pathological conditions.
Neutrophil Extracellular Traps contribute to the pathogenesis of leprosy type 2 reactions
Authors: da Silva Camila Oliveira , Dias André Alves , da Costa Nery José Augusto , de Miranda Machado Alice , Ferreira Helen , Sousa Santos João Pedro , Nadaes Natalia Rocha , Sarno Euzenir Nunes , Saraiva Elvira Maria , Schmitz Verônica , Pessolani Maria Cristina Vidal 
Published: April 2019

AbstractUp to 50% of patients with the multibacillary form of leprosy is expected to develop acute systemic inflammatory episodes known as type 2 reactions (T2R), thus aggravating their clinical status. Thalidomide rapidly improves T2R symptoms. But, due to its restricted use worldwide, novel alternative therapies are urgently needed. A hallmark of T2R lesions is the presence of a neutrophil-rich inflammatory infiltrate. In this study, the potential involvement of neutrophil extracellular traps (NETs) production in T2R pathogenesis was investigated. Abundant NETs were found in T2R skin lesions, and increased spontaneous NETs formation was observed in T2R peripheral neutrophils. Both the M. leprae whole-cell sonicate and the CpG-Hlp complex, mimicking a mycobacterial TLR9 ligand, were able to induce NETs production in vitro. Moreover, TLR9 expression was shown to be higher in T2R neutrophils, suggesting that DNA recognition via TLR9 may be one of the pathways triggering this process during T2R. Finally, treatment of T2R patients with thalidomide for 7 consecutive days resulted in decreasing all of the evaluated in vivo and ex vivo NETosis parameters. Altogether, our findings shed light on the pathogenesis of T2R, which, it is hoped, will contribute to the emergence of novel alternative therapies in the near future.Author summaryLeprosy is caused by a mycobacterium that has a predilection for skin and nerve cells. The chronic course of the disease may be interrupted by acute inflammatory episodes known as reactions, despite effective bacterial killing with antibiotics. Reactions aggravate patient’s clinical status and may become a medical emergency. Type 2 reactions (T2R) only occur in patients with high bacterial burden and is treated with thalidomide and/or corticosteroids. We are interested in understanding how inflammation is triggered and amplified during T2R. In this study we investigated the potential role of extracellular DNA released by neutrophils (known as NETs) in T2R, since they have been shown to cause inflammation. Abundant NETs were found in T2R skin lesions, and increased spontaneous NETs formation was observed in neutrophils present in the blood of T2R patients. Moreover, bacterial constituents were able to induce NETs production. Finally, treatment of T2R patients with thalidomide resulted in decreased NET formation. Altogether, our findings shed light on the pathogenesis of T2R, which, it is hoped, will contribute to the identification of biomarkers for early diagnosis and emergence of novel alternative therapies in the near future.
A dual-functional social innovation process model for low-cost houses through university-enabled initiative
Authors: Belayutham Sheila , Che Ibrahim Che Khairil Izam , Zulkifli Assrul Reedza , Ibrahim Norhati 
Published: April 2019

Purpose
The purpose of this study is to develop a dual-functional university-enabled social innovation process model on the subject of low-cost houses that addresses the distinct elements of social obligation and university teaching–learning.

Design/methodology/approach
This study has predominantly adopted a longitudinal single case study approach, where data have been collected through interviews, survey, participant observation, direct observation and document review. The case study details on the social innovation processes, which was conducted by Universiti Teknologi MARA, Malaysia.

Findings
This study has demonstrated the social innovation processes toward addressing the issue of insufficient low-cost houses, concurrently benefitting the teaching–learning dimension. Three sub-innovations have been highlighted in the developed social innovation process model, which are collaboration process, teaching–learning and design-construct innovation.

Research limitations/implications
Because the study has been based on a single prototype project, further investigation is necessary to confirm the applicability of the full-fledged model. The established social innovation process model is also suggested to be tested in other social fields.

Practical implications
The established social innovation process model has created a new perspective that enables universities to contribute in providing shelter for low-income families, simultaneously enhancing the teaching–learning dimension through experiential learning.

Social implications
The dual-functional social innovation process model provides a synergistic relationship between the university and the society. Ultimately, the model could address social issues pertaining to low-income families with the built of low-cost houses, concurrently preparing graduates who are highly marketable, which could reduce the rate of graduate unemployment in the country.

Originality/value
The development of the social innovation process model for low-cost houses through university-enabled initiative is a novel establishment, particularly for developing nations, as limited studies have been conducted in this regard. The significant insights into how university could play a role in addressing major social issues, along with their core focus (teaching–learning and research development), is a breakthrough for further diffusions of social innovation by universities.
Social media engagement behavior
Authors: Dolan Rebecca , Conduit Jodie , Frethey-Bentham Catherine , Fahy John , Goodman Steve 
Published: April 2019

Purpose
Organizations are investing heavily in social media yet have little understanding of the effects of social media content on user engagement. This study aims to determine the distinct effects of informational, entertaining, remunerative and relational content on the passive and active engagement behavior of social media users.

Design/methodology/approach
Facebook Insights and NCapture are used to extract data from the Facebook pages of 12 wine brands over a 12-month period. A multivariate linear regression analysis investigates the effects of content on consuming, contributing and creating engagement behavior.

Findings
Results reveal distinct effects of rational and emotional appeals on social media engagement behavior. Rational appeals in social media have a superior effect in terms of facilitating active and passive engagement among social media users, whereas emotional appeals facilitate passive rather than highly active engagement behavior, despite the social and interactive nature of the digital media landscape.

Research limitations/implications
Results contribute directly to understanding engagement and customer experience with social media. Further theoretical and empirical examination in this area will aid in understanding the dynamic nature of the levels of engagement within social media.

Practical implications
Findings provide managers and practitioners with guidelines and opportunities for strategic development of social media content to enhance engagement among consumers in a social media forum.

Originality/value
This study is one of the first to empirically examine the construct of social media engagement behavior. It extends the utility of dual processing theory to demonstrate how rational and emotional message appeals result in online engagement.