bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ocrelizumab phase II extension trial suggests the potential to improve the risk:benefit balance in multiple sclerosis
Authors: Baker David , Pryce Gareth , James Louisa K. , Marta Monica , Schmierer Klaus 
Published: January 2020

ABSTRACTObjectiveOcrelizumab inhibits relapsing multiple sclerosis when administered every six months. Based on potential similar memory B cell depletion mechanisms with cladribine and alemtuzumab, we hypothesised that CD20-depletion of B cells by ocrelizumab may exhibit a duration of response exceeding the current licenced treatment interval.MethodsInternet-located information from regulatory submissions and meeting reports relating to the unpublished open-label, phase II ocrelizumab extension trial (NCT00676715) were reviewed. This followed people (54-55/arm) with MS, who switched from placebo or interferon-beta to ocrelizumab for three 600mg treatment cycles (week 24, 48, 72) or people treated with ocrelizumab for four 600mg treatment cycles (week 0-72), followed by an 18 month treatment-free period.ResultsCD19+ B cells were rapidly depleted within 2 weeks and slow CD19+ B cell repopulation began about 6 months after the last infusion with median-repletion of over 15 months. The reduced annualized relapse rate during the published efficacy study appeared to be maintained in the extension study and there were no new T1 gadolinium-enhancing or T2 lesions detected in the treatment-free period. Importantly, within these extension cohorts, there appeared to be fewer adverse events and infections events.ConclusionsOcrelizumab appears to induce durable relapsing disease inhibition, within 3 treatment cycles Therefore, it may be possible to reduce the frequency of dosing to maintain efficacy, whilst limiting infection and other risks associated with continuous immunosuppression. Further studies are now clearly required to determine whether this data is robust, as few people seemed to complete the study.
Geographical Disparities in HIV Prevalence among Men Who Have Sex with Men and People Who Inject Drugs in Nigeria
Authors: Onovo Amobi , Kalaiwo Abiye , Katbi Moses , Ogorry Otse , Jaquet Antoine , Keiser Olivia 
Published: January 2020

AbstractBackgroundAssessment of geographical heterogeneity of HIV among men who have sex with men (MSM) and people who inject drugs (PWID) can usefully inform targeted HIV prevention and care strategies. We aimed to measure HIV prevalence and identify hotspots of HIV infection among MSM and PWID in Nigeria.MethodsWe included all MSM and PWID accessing HIV testing services across seven prioritized states (Lagos, Nasarawa, Akwa Ibom, Cross Rivers, Rivers, Benue and the Federal Capital Territory) in three geographic regions (North Central, South South, South West) between Oct 1, 2016 and Sept 30, 2017. We extracted data from national testing registers, georeferenced all HIV test results aggregated at the level of Local Government Areas (LGAs), and calculated HIV prevalence. We calculated and compared HIV prevalence from our study to the integrated biological and behavioral surveillance survey (IBBSS) 2014 and used global spatial autocorrelation and hotspot analysis to highlight patterns of HIV infection, and to identify areas of significant clustering of HIV cases.FindingsA positive HIV test was reported in 12.1% (95%CI 9.7-13.1) and 11.8% (95%CI 9.3-12.7) of the 26,423 MSMs and 9,474 PWIDs, respectively. Global spatial autocorrelation Moran’s I statistics revealed a clustered distribution of HIV infection among MSMs and PWIDs with a <5% and <1% likelihood that this clustered pattern could be due to chance respectively. Significant clusters of HIV infection (Getis-Ord-Gi* statistics) confined to the North Central, South-South regions were identified among MSM and PWID. Compared to the 2014 IBBSS our results suggest an increased HIV prevalence among PWID and a substantial decrease among MSM.InterpretationThis study identified geographical areas to prioritize for control of HIV infection among MSM and PWID, thus demonstrating that geographical information system technology is a useful tool to inform public health planning for interventions for epidemic control of HIV infection.FundingData used for this study was collected from Key Population program in Nigeria through PEPFAR/USAID. OK was funded by the Swiss National Science Foundation (grant no 163878).
Basal forebrain rhythmicity is modulated by the exploration phase of novel environments
Authors: Santos-Pata Diogo , Verschure Paul FMJ 
Published: January 2020

Acquaintance to novel environments requires the encoding of spatial memories and the processing of unfamiliar sensory information in the hippocampus. Cholinergic signaling promotes the stabilization of hippocampal long-term potentiation (LTP) and contributes to theta-gamma oscillations balance, which is known to be crucial for learning and memory. However, the oscillatory mechanisms by which cholinergic signals are conveyed to the hippocampus are still poorly defined. We analyzed local field potentials from the basal forebrain (BF), a major source of cholinergic projections to the hippocampus, while rats explored a novel environment, and compared the modulation of BF theta (4-10Hz) and gamma (40-80Hz) frequency bands at distinct stages of spatial exploration. We found that BF theta and gamma display learning stage-related rhythmicity and that theta-gamma coupling is stronger at the later stages of exploration, a phenomenon previously observed in the hippocampus. Overall, our results suggest that the BF-hippocampal cholinergic signaling is conveyed via the stereotypical oscillatory patterns found during mnemonic processes, which questions the origins of the learning-related rhythmic activity found in the hippocampus.KEY-POINTSBasal forebrain theta oscillations decrease their strength in function of exploration time, as observed in the hippocampus.BF gamma ripples (bursting events) are longer after learning.BF Theta-gamma coupling increases after initial spatial exploration, suggesting BF cross-frequency coupling relation to the learning stage.
Neuronal firing and waveform alterations through ictal recruitment in humans
Authors: Merricks Edward M. , Smith Elliot H. , Emerson Ronald G. , Bateman Lisa M. , McKhann Guy M. , Goodman Robert R. , Sheth Sameer A. , Greger Bradley , House Paul A. , Trevelyan Andrew J. , Schevon Catherine A. 
Published: January 2020

AbstractClinical analyses of neuronal activity during seizures, invariably using extracellular recordings, is greatly hindered by various phenomena that are well established in animal studies: changes in local ionic concentration, changes in ionic conductance, and intense, hypersynchronous firing. The first two alter the action potential waveform, whereas the third increases the “noise”; all three factors confound attempts to detect and classify single neurons (units). To address these analytical difficulties, we developed a novel template-matching based spike sorting method, which enabled identification of 1,239 single units in 27 patients with intractable focal epilepsy, that were tracked throughout multiple seizures. These new analyses showed continued neuronal firing through the ictal transition, which was defined as a transient period of intense tonic firing consistent with previous descriptions of the ictal wavefront. After the ictal transition, neurons displayed increased spike duration (p< 0.001) and reduced spike amplitude (p< 0.001), in keeping with prior animal studies; units in non-recruited territories, by contrast, showed more stable waveforms. All units returned to their pre-ictal waveforms after seizure termination. Waveshape changes were stereotyped across seizures within patients. Our analyses of single neuron firing patterns, at the ictal wavefront, showed widespread intense activation, and commonly involving marked waveshape alteration. We conclude that the distinction between tissue that has been recruited to the seizure versus non-recruited territories is evident at the level of single neurons, and that increased waveform duration and decreased waveform amplitude are hallmarks of seizure invasion that could be used as defining characteristics of local recruitment.SignificanceStatementAnimal studies consistently show marked changes in action potential waveform during epileptic discharges, but acquiring similar evidence in humans has proved difficult. Assessing neuronal involvement in ictal events is pivotal to understanding seizure dynamics and in defining clinical localization of epileptic pathology. Using a novel method to track neuronal firing, we analyzed microelectrode array recordings of spontaneously occurring human seizures, and here report two dichotomous activity patterns. In cortex that is recruited to the seizure, neuronal firing rates increase and waveforms become longer in duration and shorter in amplitude, while penumbral tissue shows stable action potentials, in keeping with the “dual territory” model of seizure dynamics.
5’ UTR variants in the quantitative trait geneHnrnph1support reduced 5’ UTR usage and hnRNP H protein as a molecular mechanism underlying reduced methamphetamine sensitivity
Authors: Ruan Qiu T. , Yazdani Neema , Reed Eric R. , Beierle Jacob A. , Peterson Lucy P. , Luttik Kimberly P. , Szumlinski Karen K. , Johnson William E. , Ash Peter E. A. , Wolozin Benjamin , Bryant Camron D. 
Published: January 2020

ABSTRACTWe previously identified a 210 kb region on chromosome 11 (50.37-50.58 Mb, mm10) containing two protein-coding genes (Hnrnph1, Rufy1) that was necessary for reduced methamphetamine-induced locomotor activity in C57BL/6J congenic mice harboring DBA/2J polymorphisms. Gene editing of a small deletion in the first coding exon supportedHnrnph1as a quantitative trait gene. We have since shown thatHnrnph1mutants also exhibit reduced methamphetamine-induced reward, reinforcement, and dopamine release. However, the quantitative trait variants (QTVs) that modulateHnrnph1function at the molecular level are not known. Nine single nucleotide polymorphisms and seven indels distinguish C57BL/6J from DBA/2J withinHnrnph1, including four variants within the 5’ untranslated region(UTR). Here, we show that a 114 kb introgressed region containingHnrnph1andRufy1was sufficient to cause a decrease in MA-induced locomotor activity. Gene-level transcriptome analysis of striatal tissue from 114 kb congenics versusHnrnph1mutants identified a nearly perfect correlation of fold-change in expression for those differentially expressed genes that were common to both mouse lines, indicating functionally similar effects on the transcriptome and behavior. Exon-level analysis (including noncoding exons) revealed decreased 5’ UTR usage ofHnrnph1and immunoblot analysis identified a corresponding decrease in hnRNP H protein in 114 kb congenic mice. Molecular cloning of theHnrnph15’ UTR containing all four variants (but none of them individually) upstream of a reporter induced a decrease in reporter signal in both HEK293 and N2a cells, thus identifying a set of QTVs underlying molecular regulation ofHnrnph1.
Designing and implementing programmable depletion in sequencing libraries with DASHit
Authors: Dynerman David , Lyden Amy , Quan Jenai , Caldera Saharai , McGeever Aaron , Dimitrov Boris , King Ryan , Cirolia Giana , Tan Michelle , Sit Rene , van den Berge Maarten , Kerstjens Huib A. M. , Faiz Alen , Christenson Stephanie , Langelier Charles , DeRisi Joe , Crawford Emily 
Published: January 2020

AbstractSince Next-Generation Sequencing produces reads uniformly subsampled from an input library, highly abundant sequences may mask interesting low abundance sequences. The DASH (Depleting Abundant Sequences by Hybridization) technique takes advantage of the programmability of CRISPR/Cas9 to deplete unwanted high-abundance sequences. Because desired depletion targets vary by sample type, here we describe DASHit, software that outputs an optimal DASH target set given a sequencing dataset, an updated DASH protocol, and show depletion results with DASHit-designed targets for three different species.
Calcium-independent lipid release from astrocytes modulates neuronal excitability
Authors: Wang Fushun , Bradshaw Heather B. , Pena Salvador , Jablonska Beata , Xavier Julia , Chittaranjan Siddharth , Gong Sheng , Li Baoman , Chandler-Militello Devin , Bekar Lane K. , Smith Nathan A. 
Published: January 2020

ABSTRACTAn accumulating amount of data suggests that Ca2+-dependent gliotransmitter release plays a key role in the modulation of neuronal networks. Here, we tested the hypothesis that in response to agonist exposure, astrocytes release lipid modulators through activation of Ca2+-independent phospholipase A2(iPLA2) activity. We found that cultured rat astrocytes treated with selective ATP and glutamatergic agonists released arachidonic acid (AA) and/or its derivatives, including the endogenous cannabinoid 2-arachidonoyl-sn-glycerol (2AG) and prostaglandin E2 (PGE2). Surprisingly, the buffering of cytosolic Ca2+resulted in a sharp increase in agonist-induced lipid release by astrocytes. In addition, the astrocytic release of PGE2increased miniature excitatory postsynaptic potentials (mEPSPs) by inhibiting the opening of neuronal Kv channels in brain slices. This study provides the first evidence showing that a Ca2+-independent pathway regulates the release of PGE2from astrocytes and further demonstrates the functional role of astrocytic lipid release in the modulation of synaptic activity.SIGNIFICANCEUntil now, most studies that implicate astrocytes in the modulation of synaptic activity have focused on Ca2+-dependent release of traditional gliotransmitters such as D-serine, ATP, and glutamate. Mobilization of intracellular stores of Ca2+occurs within a matter of seconds, but this novel Ca2+-independent lipid pathway in astrocytes could occur on a faster time scale and thus play a role in the rapid signaling processes involved in synaptic potentiation, attention, and neurovascular coupling.
The role of startle fluctuation and non-response startle reflex in tracking amygdala dynamics
Authors: Liu Mengting , Amey Rachel C. , Magerman Adam , Scott Matthew , Forbes Chad E. 
Published: January 2020

ABSTRACTThe startle reflex is considered a sensitive defensive reaction to potential threats that manifests as a unique eye blink-like pattern in the EMG. Eye blink EMG has a bell-shaped potential when startle probes are elicited, that strongly corresponds to amygdala activity. Considering how amygdala activity fluctuates over time in response to emotional and self-threatening stimuli, observing startle eyeblink size fluctuation over time could provide a cost-effective, convenient, and less resource intensive means for examining amygdala activity over time. Yet based on current standards in the literature, often startle evoked eye blink EMG values do not exhibit activity 3SDs from the mean eyeblink response, thus these trials are typically excluded from startle analyses. It stands to reason, however, that these trials may still index amygdala activity in a meaningful way. Through investigating the association between startle eyeblink amplitude, corresponding ERP amplitude, and underlying neural activity, the current study provides evidence that startle amplitudes exhibit a linear relationship with proxies for amygdala activity, e.g., N100 amplitudes and regions heavily interconnected with the amygdala. Specifically, the startle reflex correlates to large amount of brain regions in N100 time window in addition to the N100 amplitude. Thus, both valid and otherwise traditionally non-valid startle reflex responses appear to index amygdala activity and should be included accordingly. This approach could help salvage large amounts of meaningful data traditionally excluded from studies interested in amygdala responses to various stimuli over time.
A practical staging atlas to study embryonic development ofOctopus vulgarisunder controlled laboratory conditions
Authors: Astrid Deryckere , Ruth Styfhals , Erica A.G. Vidal , Eduardo Almansa , Eve Seuntjens 
Published: January 2020

AbstractBackgroundOctopus vulgarishas been an iconic cephalopod species for neurobiology research as well as for cephalopod aquaculture. It is one of the most intelligent and well-studied invertebrates, possessing both long- and short-term memory and the striking ability to perform complex cognitive tasks. Nevertheless, how the common octopus developed these uncommon features remains enigmatic.O. vulgarisfemales spawn thousands of small eggs and remain with their clutch during their entire development, cleaning, venting and protecting the eggs. In fact, eggs incubated without females usually do not develop normally, mainly due to biological contamination (fungi, bacteria, etc.). This high level of parental care might have hampered laboratory research on the embryonic development of this intriguing cephalopod.ResultsHere, we present a completely parameter-controlled artificial seawater standalone egg incubation system that replaces maternal care and allows successful embryonic development of a small-egged octopus species until hatching in a laboratory environment. We also provide a practical and detailed 1 staging atlas based on bright-field and light sheet fluorescence microscopy imaging for precise monitoring of embryonic development. The atlas has a comparative section to benchmark stages to the different scales published by Naef (1928), Arnold (1965) and Boletzky (2016). Finally, we provide methods to monitor health and wellbeing of embryos during organogenesis.ConclusionBesides introducing the study ofO. vulgarisembryonic development to a wider community, this work can be a high-quality reference for comparative evolutionary developmental biology.
Comparison of cellular Na+assays by flow fluorometry with ANG-2 and flame emission: Pitfalls in using ionophores for calibrating fluorescent probes
Authors: Yurinskaya Valentina E. , Aksenov Nikolay D. , Moshkov Alexey V. , Goryachaya Tatyana S. , Vereninov Alexey A. 
Published: January 2020

AbstractMonovalent ions, sodium in particular, are involved in fundamental cell functions, such as water balance and electric processes, intra- and intercellular signaling, cell movement, pH regulation and metabolite transport into and out of cells. Fluorescent probes are indispensable tools for monitoring intracellular sodium levels in single living cells in heterogeneous cell populations and tissues. Since the fluorescence of sodium-sensitive dyes in cells is significantly different from that in an aqueous solution, the fluorescence signal is calibratedin situby changing the concentration of extracellular sodium in the presence of ionophores, making the membrane permeable to sodium and equilibrating its intra- and extracellular concentrations. The reliability of this calibration method has not been well studied. Here, we compare the determinations of the intracellular sodium concentration by flame emission photometry and flow cytometry using the Na+-sensitive probe Asante Natrium Green-2 (ANG). The intracellular Na+concentration was altered using known ionophores or, alternatively, by blocking the sodium pump with ouabain or by causing cell apoptosis with staurosporine. The use of U937 cells cultured in suspension allowed the fluorometry of single cells by flow cytometry and flame emission analysis of samples checked for uniform cell populations. It is revealed that the ANG fluorescence of cells treated with ionophores is approximately two times lower than that in cells with the same Na+concentration but not treated with ionophores. Although the mechanism is still unknown, this effect should be taken into account when a quantitative assessment of the concentration of intracellular sodium is required. Sodium sensitive fluorescent dyes are widely used at present, and the problem is practically significant.
Germination response of invasive plants to soil burial depth and litter accumulation is species specific
Authors: Sonkoly Judit , Valkó Orsolya , Balogh Nóra , Godó Laura , Kelemen András , Kiss Réka , Miglécz Tamás , Tóth Edina , Tóth Katalin , Tóthmérész Béla , Török Péter 
Published: January 2020

AbstractQuestionsPlant invasions are considered among the biggest threats to biodiversity worldwide. In a full-factorial greenhouse experiment we analysed the effect of soil burial depth and litter cover on the germination of invasive plants. We hypothesised that (i) burial depth and litter cover affect the germination of the studied species, (ii) the effects of burial and litter cover interact with each other, and (iii) the effects are species-specific, but dependent on seed size.MethodsWe tested the germination and seedling growth of 11 herbaceous invasive species in a full-factorial experiment using four levels of seed burial depths and litter cover. We analysed the effect of burial, litter cover, and their interactions on germination, seedling length and biomass across species and at the species level.ResultsSoil burial depth and litter cover had a significant effect on the germination of the studied species, but there were considerable differences between species. We observed a general trend of species with bigger seeds being not or less seriously affected by soil burial and litter cover than smaller-seeded species. Correlations between seed weight and effect sizes mostly confirmed this general trend, but not in the case of soil burial.ConclusionsOur findings confirmed that seed size is a major driver of species’ response to litter cover and to the combined effects of litter cover and soil burial, but there is no general trend regarding the response to soil burial depth. Despite its very small seeds the germination ofCynodon dactylonwas not affected by soil burial. The germination ofAmbrosia artemisiifoliawas hampered by both soil burial and litter cover despite its relatively large seeds. Thus, specific information on species’ response to burial depth and litter accumulation is crucial when planning management or restoration in areas threatened by plant invasions.
Global comparisons of job satisfaction across occupational categories
Authors: Andrade Maureen Snow , Westover Jonathan H. 
Published: January 2020

Purpose
Job satisfaction has positive outcomes for individuals and organizations. These include decreased turnover and conflict, increased productivity, improved work quality and creativity and innovation. Determinants entail work–life balance, advancement and development opportunities, relationships with co-workers and managers, working conditions and intrinsic and extrinsic rewards, among others. Understanding these determinants across workers and contexts is critical for effective management and the achievement of organizational goals. The paper aims to discuss this issue.

Design/methodology/approach
This study, based on data from the International Social Survey Program, examines the impact of various aspects of work-life balance, rewards and work relations on job satisfaction across occupations.

Findings
Findings indicate more differences than similarities among countries and occupations with workers in managerial and professional positions experiencing the highest job satisfaction levels.

Originality/value
Although extensive research has documented the benefits and determinants of job satisfaction, it has not focused on global comparisons across occupational categories.