bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Theory of Collateral for the Lender of Last Resort*
Authors: Choi Dong Beom , Santos João A C , Yorulmazer Tanju 
Published: February 2021

Abstract
We consider a macroprudential approach to analyze the optimal lending policy for the central bank, focusing on spillover effects that policy exerts on money markets. Lending against high-quality collateral protects central banks against losses, but can adversely affect liquidity creation in markets since high-quality collateral gets locked up with the central bank rather than circulating in markets. Lending against low-quality collateral creates counterparty risk but can improve liquidity in markets. We illustrate the optimal policy incorporating these trade-offs. Contrary to what is generally accepted, lending against high-quality collateral can have negative effects, whereas it may be optimal to lend against low-quality collateral.
Targeting fronto-limbic dysfunctions via intermittent theta burst stimulation as a novel treatment for Functional Movement Disorders
Authors: Spagnolo Primavera A , Parker Jacob , Horovitz Silvina , Hallett Mark 
Published: February 2021

AbstractBackgroundNeuroimaging studies suggest that corticolimbic dysfunctions, including increased amygdala reactivity to emotional stimuli and heightened fronto-amygdala coupling, play a central role in the pathophysiology of functional movement disorders (FMD), although there is no direct causal evidence of this relationship. Transcranial magnetic stimulation (TMS) has the potential to probe and modulate brain networks implicated in neuropsychiatric disorders, including FMD. Therefore, in this proof-of-concept study, we investigated safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of FMD.MethodsSix subjects with a clinically defined diagnosis of FMD received three open-label iTBS sessions per day, for two consecutive study visits. Safety and tolerability were assessed throughout the trial. Amygdala reactivity to emotionally valenced stimuli presented during an fMRI task and fronto-amygdala connectivity at rest were evaluated at baseline and after each stimulation visit, together with subjective levels of arousal and valence in response to affective stimuli. FMD symptom severity was assessed at baseline, during treatment and 24 hours after receiving the last iTBS session.ResultsMultiples doses of iTBS were well-tolerated by all participants. Intermittent TBS significantly decreased fronto-amygdala connectivity and also influenced amygdala reactivity to emotional stimuli. These neurocircuitry changes were associated to a significant decrease in negative valence and an increase in positive valence levels following iTBS. Furthermore, we also observed a marked reduction in FMD symptom severity post stimulation.ConclusionsCorticolimbic modulation via iTBS represents a promising treatment for FMD that warrants additional research.
Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by both inactivated BBIBP-CorV and recombinant dimeric RBD ZF2001 vaccines
Authors: Huang Baoying , Dai Lianpan , Wang Hui , Hu Zhongyu , Yang Xiaoming , Tan Wenjie , Gao George F. 
Published: February 2021

AbstractRecently, the emerged and rapidly spreading SARS-CoV-2 variant of concern (VOC) 501Y.V2 with 10 amino acids in spike protein were found to escape host immunity induced by infection or vaccination. Global concerns have been raised for its potential to affect vaccine efficacy. Here, we evaluated the neutralization activities of two vaccines developed in China against 501Y.V2. One is licensed inactivated vaccine BBIBP-CorV and the other one is recombinant dimeric receptor-binding domain (RBD) vaccine ZF2001. Encouragingly, both vaccines largely preserved neutralizing titres, with slightly reduction, against 501Y.V2 authentic virus compare to their titres against both original SARS-CoV-2 and the currently circulating D614G virus. These data indicated that 501Y.V2 variant will not escape the immunity induced by vaccines targeting whole virus or RBD.
Basal-to-classical phenotypic switch of pancreatic cancer cells upon integration into the duodenal epithelium
Authors: Bozóky Benedek , Fernández Moro Carlos , Strell Carina , Ernberg Ingemar , Szekely Laszlo , Gerling Marco , Bozóky Béla 
Published: February 2021

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes can be defined that differ in prognosis. Single-cell sequencing has recently revealed that these subtypes coexist in individual tumors. However, the contribution of either clonal heterogeneity or microenvironmental cues to subtype heterogeneity is unclear. Here, we report the tumor phenotype dynamics in a cohort of patients in whom PDAC infiltrated the duodenal wall. Using multiplex immunohistochemistry, we show that PDAC cells revert to non-destructive growth and undergo differentiation towards the classical subtype upon integration into the duodenal epithelium. Our results tightly link microenvironmental cues to the PDAC molecular subtype and open the door to a systematic investigation of microenvironmental control in human pancreatic cancer.
Maladaptive cue-controlled cocaine-seeking habits promote increased relapse severity in rats
Authors: Fouyssac Maxime , Peña-Oliver Yolanda , Puaud Mickaёl , Lim Nicole , Giuliano Chiara , Everitt Barry J , Belin David 
Published: February 2021

AbstractThe inflexible pursuit of drug-seeking and great tendency to relapse that characterize addiction has been associated with the recruitment of the dorsolateral striatum-dependent habit system. However, the mechanisms by which maladaptive drug-seeking habits influence subsequent relapse are obscure. Here, we show that rats with a long history of cocaine-seeking, controlled by drug-paired cues and mediated by the habit system, show highly exacerbated drug-seeking at relapse that is not mediated by cocaine withdrawal. This heightened tendency to relapse is underpinned by transient engagement of the dorsomedial striatum goal-directed system and reflects emergent negative urgency resulting from the prevention of enacting the seeking habit during abstinence. These results reveal a novel mechanism underlying the pressure to relapse and indicate a target for preventing it.One Sentence SummaryInstrumental deprivation triggers flexibility in the well-established cue-controlled cocaine-seeking behaviour.
Distinct neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex
Authors: Hill Paul F. , Seger Sarah E. , Yoo Hye Bin , King Danielle R. , Lega Bradley C. , Rugg Michael D. 
Published: February 2021

AbstractFunctional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood-oxygen-level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modelling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70-150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30-70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex.Significance StatementThe blood-oxygen-level-dependent (BOLD) signal forms the basis of fMRI but provides only an indirect measure of neural activity. Task-related modulation of BOLD signals are typically equated with changes in gamma-band activity; however, relevant empirical evidence comes largely from the neocortex. We examined neurophysiological correlates of the BOLD signal in the hippocampus, where the differing neural architecture might result in a different relationship between the respective signals. We identified a positive relationship between encoding-related changes in BOLD and gamma-band activity in frontal, temporal, and parietal cortex. This effect was reversed in the hippocampus, where BOLD and gamma-band effects negatively covaried. These results suggest regional variability in the transfer function between neural activity and the BOLD signal in the hippocampus and neocortex.
Spray-induced gene silencing for disease control is dependent on the efficiency of pathogen RNA uptake
Authors: Qiao Lulu , Lan Chi , Capriotti Luca , Ah-Fong Audrey , Sanchez Jonatan Nino , Hamby Rachael , Heller Jens , Zhao Hongwei , Glass N. Louise , Judelson Howard S. , Mezzetti Bruno , Niu Dongdong , Jin Hailing 
Published: February 2021

AbstractRecent discoveries show that fungi can take up environmental RNA, which can then silence fungal genes through environmental RNA interference. This discovery prompted the development ofSpray-InducedGeneSilencing (SIGS) for plant disease management. In this study, we aimed to determine the efficacy of SIGS across a variety of eukaryotic microbes. We first examined the efficiency of RNA uptake in multiple pathogenic and non-pathogenic fungi, and an oomycete pathogen. We observed efficient double-stranded RNA (dsRNA) uptake in the fungal plant pathogensBotrytis cinerea,Sclerotinia sclerotiorum,Rhizoctonia solani,Aspergillus niger, andVerticillium dahliae, but no uptake inColletotrichum gloeosporioides, and weak uptake in a beneficial fungus,Trichoderma virens. For the oomycete plant pathogen,Phytophthora infestans, RNA uptake was limited, and varied across different cell types and developmental stages. Topical application of dsRNA targeting virulence-related genes in the pathogens with high RNA uptake efficiency significantly inhibited plant disease symptoms, whereas the application of dsRNA in pathogens with low RNA uptake efficiency did not suppress infection. Our results have revealed that dsRNA uptake efficiencies vary across eukaryotic microbe species and cell types. The success of SIGS for plant disease management can largely be determined by the pathogen RNA uptake efficiency.
Investigating the validity of the Strengths and Difficulties Questionnaire to assess ADHD in young adulthood
Authors: Riglin Lucy , Agha Sharifah Shameem , Eyre Olga , Jones Rhys Bevan , Wootton Robyn E , Thapar Ajay K , Collishaw Stephan , Stergiakouli Evie , Langley Kate , Thapar Anita 
Published: February 2021

AbstractAttention Deficit Hyperactivity Disorder (ADHD) symptoms typically onset early in development and persist into adulthood for many. Robust investigation of symptom continuity and discontinuity requires repeated assessments using the same measure, but research is lacking into whether measures used to assess ADHD symptoms in childhood are also valid in adulthood. The Strengths and Difficulties Questionnaire (SDQ) has been widely used to measure ADHD symptoms in children, but little is known about its utility to measure ADHD in adulthood. We used Receiver Operating Characteristic (ROC) curve analyses to examine the validity of the SDQ hyperactivity/ADHD subscale to distinguish between cases and non-cases of DSM-5 ADHD classified using the Barkley Adult ADHD Rating Scale-IV (BAARS-IV) at age 25 years in a UK population cohort (N=4121). Analyses suggested that the SDQ ADHD subscale had high accuracy in distinguishing ADHD cases from non-cases in young adulthood (area under the curve=0.90, 95% CI=0.87-0.93) and indicated a lower cut-point for identifying those who may have an ADHD diagnosis in this age group compared to that currently recommended for younger ages.Our findings suggest that the SDQ is suitable for ADHD research across different developmental periods, which will aid the robust investigation of ADHD from childhood to young adulthood.HighlightsThe SDQ is widely used to measure ADHD symptoms in childrenWe investigated the validity of the SDQ to assess ADHD at age 25 yearsThe SDQ ADHD subscale had high accuracy in distinguishing DSM-5 ADHD cases from non-casesA lower cut-point is needed to identify ADHD diagnosis in young adulthood compared to younger agesThe SDQ is appropriate for ADHD research across different development periods
Adult vaccination in Brazil: a cross-sectional survey on physicians’ prescription habits
Authors: Serra Fernando B , Ribeiro Diogo , Batista Paula M , Moreira Thais N F 
Published: February 2021

ABSTRACTOBJECTIVETo characterize adult and older adult vaccination practices of physicians from various medical specialties in Brazil, identify the barriers influencing prescription of vaccines to these populations, and evaluate the physicians’ knowledge on routinely prescribed vaccines.METHODSCross-sectional survey conducted in Brazil between June-August 2018. Eligible physicians included those from general practice/family medicine, geriatrics, cardiology, gynecology, endocrinology, infectious disease and pulmonology. The survey’s questions addressed the physicians’ prescription habits, sociodemographic and clinical practice characteristics, barriers to vaccines’ prescription to adult and older adult patients, and physicians’ knowledge regarding routinely prescribed vaccines. The study focused on the vaccines recommended by the Brazilian Society of Immunization (SBIm) for adults and older adults. Study sample was stratified according to the number of physicians per specialty and Brazilian region.RESULTSA total of 1068 surveys were completed. The vaccines prescribed by the highest proportions of physicians were Influenza (>90% of physicians for adults and older adults), Hepatitis B (adults: 87%; older adults: 59%) and Yellow Fever (adults: 77.7%; older adults: 58.5%). Underprescription was reported by less than 20% of prescribing physicians for all adult and older adult recommended vaccines. The most common barriers to vaccination were the high vaccine cost, lack of time during appointments and lack of patient interest. Knowledge on target populations, dosage schedule and availability in the Unified Public Health System (SUS) was generally low.CONCLUSIONSThe results showed a considerable variability of prescribing habits across recommended vaccines and medical specialties. Although most prescribing physicians seem to be aware of the importance of adult and older adults vaccination, knowledge deficits on vaccines’ target populations, dosage schedule and availability in the SUS may hamper their ability to prescribe vaccines to all patients with an indication.
Microglia drive pockets of neuroinflammation in middle age
Authors: Moca Eric N. , Lecca Daniela , Hope Keenan T. , Tweedie David , Sidhu Shanaya , Masukawa Lindsay , Sitoy Hannah , Mathew Rose , Saban Daniel R. , Greig Nigel H. , De Biase Lindsay M. 
Published: February 2021

ABSTRACTDuring aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to insults, positioning these cells to have profound impact on the functional integrity of nearby neurons. We and others recently showed that microglial attributes differ significantly across brain regions and CNS insults in young adult mice. However, the degree to which microglial properties vary during aging is largely unexplored. Here, we analyze and manipulate microglial aging within the basal ganglia, brain circuits that exhibit prominent regional microglial heterogeneity and where neurons are vulnerable to functional decline and neurodegenerative disease. We demonstrate that microglia in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) exhibit unique and premature responses to aging, compared to microglia elsewhere. This is associated with ‘pockets’ of VTA/SNc neuroinflammation that are likely to compromise local synaptic function as early as middle age. Surprisingly, these early aging responses of VTA and SNc microglia do not appear to be driven by systemic inflammation, local neuron death, or early responses of astrocytes to aging. Finally, CX3CR1 receptor knockout can exacerbate and microglial ablation/repopulation can suppress early VTA microglial aging; these manipulations have been shown to affect brain-wide microglial aging, and our data demonstrate that their impact is not uniform throughout the CNS. Our findings reveal a previously unappreciated regional variation in the onset and magnitude of microglial aging responses and suggest that there may be important links between local microglial aging and vulnerability of nearby neurons to functional decline and disease.
Validation and classification of RNA binding proteins identified by mRNA interactome capture
Authors: Vaishali  , Dimitrova-Paternoga Lyudmila , Haubrich Kevin , Sun Mai , Ephrussi Anne , Hennig Janosch 
Published: February 2021

AbstractRNA binding proteins (RBPs) take part in all steps of the RNA life cycle and are often essential for cell viability. Most RBPs have a modular organization and comprise a set of canonical RNA binding domains. However, in recent years a number of high-throughput mRNA interactome studies on yeast, mammalian cell lines and whole organisms have uncovered a multitude of novel mRNA interacting proteins that lack classical RNA binding domains. Whereas a few have been confirmed to be direct and functionally relevant RNA binders, biochemical and functional validation of RNA binding of most others is lacking. In this study, we employed a combination of NMR spectroscopy and biochemical studies to test the RNA binding properties of six putative RNA binding proteins. Half of the analysed proteins showed no interaction, whereas the other half displayed weak chemical shift perturbations upon titration with RNA. One of the candidates we found to interact weakly with RNA in vitro is Drosophila melanogaster End binding protein 1 (EB1), a master regulator of microtubule plus-end dynamics. Further analysis showed that EB1’s RNA binding occurs on the same surface as that with which EB1 interacts with microtubules. RNA immunoprecipitation and colocalization experiments suggest that EB1 is a rather non-specific, opportunistic RNA binder. Our data suggest that care should be taken when embarking on an RNA binding study involving these unconventional, novel RBPs, and we recommend initial and simple in vitro RNA binding experiments.
Dynamic histone acetylation in floral volatile synthesis and emission in petunia flowers
Authors: Patrick Ryan M. , Huang Xing-Qi , Dudareva Natalia , Li Ying 
Published: February 2021

ABSTRACTBiosynthesis of secondary metabolites relies on primary metabolic pathways to provide precursors, energy, and cofactors, thus requiring coordinated regulation of primary and secondary metabolic networks. However, to date it remains largely unknown how this coordination is achieved. Using Petunia hybrida flowers, which emit high levels of phenylpropanoid/benzenoid volatile organic compounds (VOCs), we uncovered genome-wide dynamic deposition of histone H3 lysine 9 acetylation (H3K9ac) during anthesis as an underlying mechanism to coordinate primary and secondary metabolic networks. The observed epigenome reprogramming is accompanied by transcriptional activation, at gene loci involved in primary metabolic pathways that provide precursor phenylalanine, as well as secondary metabolic pathways to produce volatile compounds. We also observed transcriptional repression among genes involved in alternative phenylpropanoid branches that compete for metabolic precursors. We show that GNAT family histone acetyltransferase(s) (HATs) are required for the expression of genes involved in VOC biosynthesis and emission, by using chemical inhibitors of HATs, and by knocking down a specific HAT, ELP3, through transient RNAi. Together, our study supports that chromatin level regulatory mechanisms may play an essential role in activating primary and secondary metabolic pathways to regulate VOC synthesis in petunia flowers.HIGHLIGHTOur study shows that posttranslational modification of histones is essential for regulating the biosynthesis and emission of floral scent compounds, thus providing insights into chromatin level regulation of secondary metabolism.
Single calcium channel nanodomains drive presynaptic calcium entry at lamprey reticulospinal presynaptic terminals
Authors: Ramachandran S , Rodgriguez S , Potcoava M , Alford S 
Published: February 2021

AbstractSynchronous neurotransmission is central to efficient information transfer in neural circuits, requiring precise coupling between action potentials, Ca2+entry and neurotransmitter release. However, determinations of Ca2+requirements for release, which may originate from entry through single voltage-gated Ca2+channels, remain largely unexplored in simple active zone synapses common in the nervous system. Understanding these requirements is key to addressing Ca2+channel and synaptic dysfunction underlying numerous neurological and neuropsychiatric disorders. Here, we present single channel analysis of evoked active zone Ca2+entry, using cell-attached patch clamp and lattice light sheet microscopy over active zones at single central lamprey reticulospinal presynaptic terminals. Our findings show a small pool (mean of 23) of Ca2+channels at each terminal, comprising subtypes N-type (CaV2.2), P/Q-type (CaV2.1) and R-type (CaV2.3), available to gate neurotransmitter release. Significantly, of this pool only 1-6 (mean of 4) channels open upon depolarization. High temporal fidelity lattice light sheet imaging reveals AP-evoked Ca2+transients exhibiting quantal amplitude variations between action potentials and stochastic variation of precise locations of Ca2+entry within the active zone. Further, Ca2+channel numbers at each active zone correlate to the number of presynaptic primed synaptic vesicles. Together, our findings indicate 1:1 association of Ca2+channels with primed vesicles, suggesting Ca2+entry via as few as one channel may trigger neurotransmitter release.
Co-linear Chaining with Overlaps and Gap Costs
Authors: Jain Chirag , Gibney Daniel , Thankachan Sharma V. 
Published: February 2021

AbstractCo-linear chaining has proven to be a powerful heuristic for finding near-optimal alignments of long DNA sequences (e.g., long reads or a genome assembly) to a reference. It is used as an intermediate step in several alignment tools that employ a seed-chain-extend strategy. Despite this popularity, efficient subquadratic-time algorithms for the general case where chains support anchor overlaps and gap costs are not currently known. We present algorithms to solve the co-linear chaining problem with anchor overlaps and gap costs inÕ(n) time, wherendenotes the count of anchors. We also establish the first theoretical connection between co-linear chaining cost and edit distance. Specifically, we prove that for a fixed set of anchors under a carefully designed chaining cost function, the optimal ‘anchored’ edit distance equals the optimal co-linear chaining cost. Finally, we demonstrate experimentally that optimal co-linear chaining cost under the proposed cost function can be computed orders of magnitude faster than edit distance, and achieves correlation coefficient above 0.9 with edit distance for closely as well as distantly related sequences.