bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can a microdynamic approach to sleep-onset imagery solve the overabundance problem of dreaming? Commentary on Tore Nielsen’s “Microdream neurophenomenology”
Authors: Windt Jennifer M 
Published: June 2019

Abstract
Nielsen proposes that a microdynamic approach to experiences occurring in the earliest stages of sleep onset, which he calls microdreams, can shed light on the process of dream imagery formation. I discuss microdreams in the context of simulation views, in which dreaming is defined as the immersive experience of a virtual world centered on a virtual self. I also evaluate his proposal to expand the dimensions included in the oneiragogic spectrum by kinesis. I conclude that while a subset of microdreams might not fulfill the conditions to count as even minimal dreams, their investigation can nonetheless help address key questions in dream research and may even constitute a distinctive pathway to the generation of full-fledged dreaming.
Tort Liability for Belligerent Wrongs
Authors: Abraham Haim 
Published: June 2019

Abstract
Most legal systems deny civilians a right to compensation for losses they sustain during belligerent activities. Arguments for recognising such a right are usually divorced, to various degrees, from the moral and legal underpinnings of the notion of inflicting a wrongful loss under either international humanitarian law or domestic tort law. My aim in this article is to advance a novel account of states’ tortious liability for belligerent wrongdoing, drawing on both international humanitarian law and corrective justice approaches to domestic tort law. Structuring my account on both frameworks, I argue that some of the losses that states inflict during war are private law wrongs that establish a claim of compensation in tort. Only in cases where the in bello principles are observed can losses to person and property be justified and non-wrongful. Otherwise, they constitute wrongs, which those who inflict them have duties of corrective justice to repair.
Knockdown of Arabidopsis ROOT UVB SENSITIVE4 Disrupts Anther Dehiscence by Suppressing Secondary Thickening in the Endothecium
Authors: Zhao Shu-Qing , Li Wen-Chao , Zhang Yi , Tidy Alison C , Wilson Zoe A 
Published: June 2019

AbstractROOT UV-B SENSITIVE4 (RUS4) encodes a protein with no known function that contains a conserved Domain of Unknown Function 647 (DUF647). The DUF647-containing proteins RUS1 and RUS2 have previously been associated with root UV-B-sensing pathway that plays a major role in Arabidopsis early seedling morphogenesis and development. Here, we show that RUS4 knockdown Arabidopsis plants, referred to as amiR-RUS4, were severely reduced in male fertility with indehiscent anthers. Light microscopy of anther sections revealed a significantly reduced secondary wall thickening in the endothecium of amiR-RUS4 anthers. We further show that the transcript abundance of the NAC domain genes NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1) and NST2, which have been shown to regulate the secondary cell wall thickenings in the anther endothecium, were dramatically reduced in the amiR-RUS4 floral buds. Expression of the secondary cell wall-associated MYB transcription factor genes MYB103 and MYB85 were also strongly reduced in floral buds of the amiR-RUS4 plants. Overexpression of RUS4 led to increased secondary thickening in the endothecium. However, the rus4-2 mutant exhibited no obvious phenotype. Promoter-GUS analysis revealed that the RUS4 promoter was highly active in the anthers, supporting its role in anther development. Taken together, these results suggest that RUS4, probably functions redundantly with other genes, may play an important role in the secondary thickening formation in the anther endothecium by indirectly affecting the expression of secondary cell wall biosynthetic genes.
Representative Group Styles: How Ally Immigrant Rights Organizations Promote Immigrant Involvement
Authors: Yukich Grace , Fulton Brad R , Wood Richard L 
Published: June 2019

AbstractWhy are some organizations more successful than others at involving socially diverse groups of people? Previous research emphasizes the role representative leaders play in recruiting diverse constituencies. This study extends that research by analyzing how an organization’s group style—its customs that shape everyday interactions—influences constituent involvement by either bridging or reinforcing social divides. Our multi-method approach examines ally immigrant rights organizations to assess the relationship between their group styles and their ability to involve immigrants. Ethnographic data reveal that divergent levels of immigrant involvement in two organizations can be explained by differences in the organizations’ group styles—specifically, differences in their religious, class-based, and linguistic practices. Original survey data from a national sample of ally organizations demonstrate the generalizability of our findings. Our analysis shows how having an immigrant-friendly group style can promote immigrant involvement, indicating that an organization’s style is associated with its social composition. Having representative leaders from immigrant groups, though positively associated with immigrant involvement, is insufficient for sustaining immigrant involvement; group style can moderate the effect of having representative leaders. This research suggests that organizations seeking to recruit and retain a diverse social base could benefit from cultivating a representative group style.
Indirect Sexual Selection Drives Rapid Sperm Protein Evolution
Authors: Wilburn Damien B. , Tuttle Lisa M. , Klevit Rachel E. , Swanson Willie J. 
Published: June 2019

AbstractSexual selection can explain rapid evolution of fertilization proteins, yet sperm proteins evolve rapidly even if they are not directly involved in fertilization. Here we demonstrate that FITZAP, an intrinsically disordered sperm protein in the marine mollusk abalone, exploits differences in the intracellular and oceanic ionic environments to package the fertilization protein lysin at extraordinary concentrations inside sperm by forming Fuzzy Interacting Transient Zwitterion (FITZ) complexes. FITZAP binds lysin at the same protein interface as its egg receptor VERL, and as sexual selection rapidly alters the lysin-VERL interface, FITZAP coevolves rapidly to maintain lysin binding. Consequently, FITZAP-lysin interactions exhibit a similar species-specificity as lysin-VERL interactions. Thus, tethered molecular arms races driven by sexual selection can generally explain rapid sperm protein evolution.One Sentence SummaryStructural study of sperm proteins reveals a novel protein packaging/dispersion system embedded in a coevolutionary arms race.
NINscope: a versatile miniscope for multi-region circuit investigations
Authors: de Groot Andres , van den Boom Bastijn J.G. , van Genderen Romano M. , Coppens Joris , van Veldhuijzen John , Bos Joop , Hoedemaker Hugo , Negrello Mario , Willuhn Ingo , De Zeeuw Chris I. , Hoogland Tycho M. 
Published: June 2019

AbstractMiniaturized fluorescence microscopes (miniscopes) have been instrumental to monitor neural activity during unrestrained behavior and their open-source versions have helped to distribute them at an affordable cost. Generally, the footprint and weight of open-source miniscopes is sacrificed for added functionality. Here, we present NINscope: a light-weight, small footprint, open-source miniscope that incorporates a high-sensitivity image sensor, an inertial measurement unit (IMU), and an LED driver for an external optogenetic probe. We highlight the advantages of NINscope by performing the first simultaneous cellular resolution (dual scope) recordings from cerebellum and cerebral cortex in unrestrained mice, revealing that the activity of both regions generally precedes the onset of behavioral acceleration. We further demonstrate the optogenetic stimulation capabilities of NINscope and show that cerebral cortical activity can be driven strongly by cerebellar stimulation. To validate the performance of our miniscope to image from deep-brain regions, we recorded in the dorsal striatum and, using the IMU to assess turning movements, replicate previous studies that show encoding of action space in this subcortical region. Finally, we combine optogenetic stimulation of distinct cortical regions projecting to the dorsal striatum, to probe functional connectivity. In combination with cross-platform control software, NINscope is a versatile addition to the expanding toolbox of open-source miniscopes and will aid multi-region circuit investigations during unrestrained behavior.
Noradrenergic but not dopaminergic neurons signal task state changes and predict re-engagement after a failure
Authors: Jahn Caroline I , Varazzani Chiara , Sallet Jérôme , Walton Mark E , Bouret Sébastien 
Published: June 2019

AbstractThe two catecholamines, noradrenaline and dopamine, have been shown to play comparable roles in behaviour. Both noradrenergic and dopaminergic neurons respond to salient cues predicting reward availability and to stimulus novelty, and shape action selection strategies. However, their roles in motivation have seldom been directly compared. We therefore examined the activity of noradrenergic neurons in the locus coeruleus and putative midbrain dopaminergic neurons in monkeys cued to perform effortful actions for rewards. The activity in both regions correlated with the likelihood of engaging with a presented option. By contrast, only noradrenaline neurons were also (i) predictive of engagement in a subsequent trial following a failure to engage and (ii) sensitive to the task state change, the discovery of the new task condition in unrepeated trials. This indicates that while dopamine is primarily important for the promotion of actions directed towards currently available rewards, noradrenergic neurons play a crucial complementary role in mobilizing resources to promote future engagement.
MERTK on mononuclear phagocytes regulates T cell antigen recognition at autoimmune and tumor sites
Authors: Lindsay Robin S. , Whitesell Jennifer C. , Dew Kristen E. , Rodriguez Erika , Sandor Adam M. , Tracy Dayna , Yannacone Seth F. , Basta Brittany N. , Jacobelli Jordan , Friedman Rachel S. 
Published: June 2019

AbstractUnderstanding mechanisms of immune regulation is key to developing immunotherapies for autoimmunity and cancer. We examined the role of mononuclear phagocytes during peripheral T cell regulation in type 1 diabetes and melanoma. MERTK expression and activity in mononuclear phagocytes in the pancreatic islets, promoted islet T cell regulation, resulting in reduced sensitivity of T cell scanning for cognate antigen in pre-diabetic islets. MERTK-dependent regulation led to reduced T cell activation and effector function at the disease site in the islets and prevented rapid progression of type 1 diabetes. In human islets, MERTK-expressing cells were increased in remaining insulin-containing islets of type 1 diabetic patients, suggesting that MERTK protects the islets from autoimmune destruction. MERTK also regulated T cell arrest in melanoma tumors. These data indicate that MERTK signaling in mononuclear phagocytes drives T cell regulation at inflammatory disease sites in peripheral tissues through a mechanism that reduces the sensitivity of scanning for antigen leading to reduced responsiveness to antigen.
Reliable longitudinal brain age prediction in stroke patients: Associations with cognitive function and response to cognitive training
Authors: Richard Geneviève , Kolskår Knut , Ulrichsen Kristine M. , Kaufmann Tobias , Alnæs Dag , Sanders Anne-Marthe , Dørum Erlend S. , Sánchez Jennifer Monereo , Petersen Anders , Ihle-Hansen Hege , Nordvik Jan Egil , Westlye Lars T. 
Published: June 2019

AbstractCognitive deficits are important predictors for outcome, independence and quality of life after stroke, but often remain unnoticed and unattended because other impairments are more evident. Computerized cognitive training (CCT) is among the candidate interventions that may alleviate cognitive difficulties, but the evidence supporting its feasibility and effectiveness is scarce, partly due to the lack of tools for outcome prediction and monitoring. Magnetic resonance imaging (MRI) provides candidate markers for disease monitoring and outcome prediction. By integrating information not only about lesion extent and localization, but also regarding the integrity of the unaffected parts of the brain, advanced MRI provides relevant information for developing better prediction models in order to tailor cognitive intervention for patients, especially in a chronic phase.Using brain age prediction based on MRI based brain morphometry and machine learning, we tested the hypotheses that stroke patients with a younger-appearing brain relative to their chronological age perform better on cognitive tests and benefit more from cognitive training compared to patients with an older-appearing brain. In this randomized double-blind study, 54 patients who suffered mild stroke (>6 months since hospital admission, NIHSS<7 at hospital discharge) underwent 3-weeks CCT and MRI before and after the intervention. In addition, patients were randomized to one of two groups receiving either active or sham transcranial direct current stimulation (tDCS). We tested for main effects of brain age gap (estimated age – chronological age) on cognitive performance, and associations between brain age gap and task improvement. Finally, we tested if longitudinal changes in brain age gap during the intervention were sensitive to treatment response. Briefly, our results suggest that longitudinal brain age prediction based on automated brain morphometry is feasible and reliable in stroke patients. However, no significant association between brain age and both performance and response to cognitive training were found.
The development and characterization of an scFv-Fc fusion based gene therapy to reduce the psychostimulant effects of methamphetamine abuse
Authors: Hay Charles E. , Ewing Laura E. , Hambuchen Michael D. , Zintner Shannon M. , Small Juliana C. , Bolden Chris T. , Fantegrossi William E , Margaritis Paris , Owens S. Michael , Peterson Eric C. 
Published: June 2019

AbstractMethamphetamine (METH) continues to be amongst the most addictive and abused drugs in the US. Unfortunately, there are currently no FDA approved pharmacological treatments for METH substance abuse disorder. As an alternative approach, we have previously explored the use of Adeno-associated viral (AAV) mediated gene transfer of an anti-METH monoclonal antibody. Here, we advance our approach by generating a novel anti-METH scFv-Fc fusion construct (7F9-Fc), packaged into AAV serotype 8 vector (called AAV-scFv-Fc), and tested in vivo and ex vivo. A range of doses (1 × 1010. 1 × 1011, and 1 × 1012 vector copies(vc)/mouse) were administered to mice, which exhibited a dose-dependent expression of 7F9-Fc in serum with peak circulating concentrations of 48, 1785, and 3,831 μg/ml. The dose of 1 × 1012 vc/mouse was further tested in METH locomotor and biodistribution studies to determine the efficacy of the antibody protection. Expressed 7F9-Fc exhibited high affinity binding, 17 nM, to METH. Between days 21 and 35 after vector administration, the 7F9-Fc gene therapy significantly reduced the effects of METH in locomotor assays following administration of moderate and high doses of subcutaneous METH, 3.1 and 9.4 mg/kg respectively. On day 116 post-AAV administration, mice expressing 7F9-Fc sequestered over 2.5 times more METH into the serum than vehicle mice, and METH concentrations in the brain were reduced by 1.2 times compared to vehicle mice. Taken together, these data suggest that a AAV-delivered anti-METH Fc fusion antibody could be a design for persistently reducing concentrations of METH in the CNS.Significance StatementIn this manuscript, we describe the use of a novel anti-METH scFv-Fc fusion protein delivered in mice using gene therapy. The results suggest that the gene therapy delivery system can lead to the production of enough antibody to mitigate METH’s psychostimulant effects in mice over an extended time period.
Dual-plane 3-photon microscopy with remote focusing
Authors: Takasaki Kevin T. , Tsyboulski Dmitri , Waters Jack 
Published: June 2019

Abstract3-photon excitation enables in vivo fluorescence microscopy deep in densely labeled and highly scattering samples. To date, 3-photon excitation has been restricted to scanning a single focus, limiting the speed of volume acquisition. Here, for the first time to our knowledge, we implemented and characterized dual-plane 3-photon microscopy with temporal multiplexing and remote focusing, and performed simultaneous in vivo calcium imaging of two planes deep in the cortex of a pan-excitatory GCaMP6s transgenic mouse. This method is a straightforward and generalizable modification to single-focus 3PE systems, doubling the rate of volume (column) imaging with off-the-shelf components and minimal technical constraints.
Engineered full-length Fibronectin-based hydrogels sequester and present growth factors to promote regenerative responses in vitro and in vivo
Authors: Trujillo Sara , Gonzalez-Garcia Cristina , Rico Patricia , Reid Andrew , Windmill James , Dalby Matthew J. , Salmeron-Sanchez Manuel 
Published: June 2019

AbstractExtracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro and can recapitulate certain ECM functions that support cell growth and differentiation. However, ECM-derived matrices suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed synthetic matrices that can also recapitulate ECM roles. Synthetic matrices have certain limitations as they use synthetic peptides or fragments whereas the ECM consists of full proteins. Here, we report the development of degradable, PEG-based hydrogels of controlled stiffness that incorporate full-length fibronectin (FN) to enable solid-phase presentation of growth factors in a physiological manner. We demonstrate, in vitro and in vivo, the effect of incorporating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), in these hydrogels to enhance angiogenesis and bone regeneration, respectively. We show that the solid-state presentation of growth factors enables very low growth factor doses to achieve regenerative effects.
Aggregation of CAT tails blocks their degradation and causes proteotoxicity in S. cerevisiae
Authors: Sitron Cole S. , Park Joseph H. , Giafaglione Jenna M. , Brandman Onn 
Published: June 2019

AbstractThe Ribosome-associated Quality Control (RQC) pathway co-translationally marks incomplete polypeptides from stalled translation with two signals that trigger their proteasome-mediated degradation. The E3 ligase Ltn1 adds ubiquitin and Rqc2 directs the large ribosomal subunit to append carboxy-terminal alanine and threonine residues (CAT tails). When excessive amounts of incomplete polypeptides evade Ltn1, CAT-tailed proteins accumulate and can self-associate into aggregates. CAT tail aggregation has been hypothesized to either protect cells by sequestering potentially toxic incomplete polypeptides or harm cells by disrupting protein homeostasis. To distinguish between these possibilities, we modulated CAT tail aggregation in Saccharomyces cerevisiae with genetic and chemical tools to analyze CAT tails in aggregated and un-aggregated states. We found that enhancing CAT tail aggregation induces proteotoxic stress and antagonizes degradation of CAT-tailed proteins, while inhibiting aggregation reverses these effects. Our findings suggest that CAT tail aggregation harms RQC-compromised cells and that preventing aggregation can mitigate this toxicity.
Monosomes actively translate synaptic mRNAs in neuronal processes
Authors: Biever Anne , Glock Caspar , Tushev Georgi , Ciirdaeva Elena , Langer Julian D. , Schuman Erin M. 
Published: June 2019

AbstractIn order to deal with their huge volume and complex morphology, neurons localize mRNAs and ribosomes near synapses to produce proteins locally. A relative paucity of polyribosomes (considered the active sites of translation) detected in electron micrographs of neuronal processes (axons and dendrites), however, has suggested a rather limited capacity for local protein synthesis. Polysome profiling together with ribosome footprinting of microdissected synaptic regions revealed that a surprisingly high number of dendritic and/or axonal transcripts were predominantly associated with monosomes (single ribosomes). Contrary to prevailing views, the neuronal monosomes were in the process of active protein synthesis (e.g. they exhibited elongation). Most mRNAs showed a similar translational status in both compartments, but some transcripts exhibited differential ribosome occupancy in the somata and neuropil. Strikingly, monosome-preferred transcripts often encoded high-abundance synaptic proteins. This work suggests a significant contribution of monosome translation to the maintenance of the local neuronal proteome. This mode of translation can presumably solve some of restricted space issues (given the large size of polysomes) and also increase the diversity of proteins made from a limited number of ribosomes available in dendrites and axons.
A survey of antenatal and peripartum provision of information on analgesia and anaesthesia
Authors: Brinkler R. , Edwards Z. , Abid S. , Oliver C. M. , Lo Q. , Stewart A. ,   the Pan‐London Peri‐operative Audit and research Network (PLAN)
Published: June 2019

SummaryPregnant women should receive information about what they might expect to experience during their delivery. Despite this, research shows many women are inadequately prepared for anaesthetic interventions during labour. We surveyed 903 postnatal women across 28 Greater London hospitals about: the analgesic and anaesthetic information that they recalled receiving during pregnancy and delivery; their confidence to make decisions on analgesia; and their satisfaction with the analgesia used. Wide variation was observed between hospitals. Overall, 67 of 749 (9.0%) women recalled receiving antenatal information covering all aspects of labour analgesia, and 108 of 889 (12.1%) covering anaesthesia for caesarean section. Regarding intrapartum information, 256 of 415 (61.7%) respondents recalled receiving thorough information before epidural insertion for labour analgesia, and 102 of 370 (27.6%) before anaesthesia for caesarean section. We found that 620 of 903 (68.7%) women felt well enough informed to be confident in their analgesic choices, and 675 of 903 (74.8%) stated that their analgesia was as expected or better. Receiving information verbally, regardless of provider, was the factor most strongly associated with respondents recalling receiving full information: odds ratio (95%CI) for labour analgesia 20.66 (8.98–47.53; p < 0.0001); epidural top‐up for caesarean section 5.93 (1.57–22.35; p = 0.01); and general anaesthesia for caesarean section 12.39 (2.18–70.42; p = 0.01). A large proportion of respondents did not recall being fully informed before an anaesthetic intervention. Collaboration with current antenatal service providers, both in promoting information delivery and providing resources to assist with delivery, could improve the quality of information offered and women's retention of that information.