bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithium ions display weak interaction with amyloid-beta (Aβ) peptides and have minor effects on their aggregation
Authors: Berntsson Elina , Paul Suman , Vosough Faraz , Sholts Sabrina B. , Jarvet Jüri , Roos Per M. , Barth Andreas , Gräslund Astrid , Wärmländer Sebastian K. T. S. 
Published: January 2021

AbstractAlzheimer’s disease (AD) is an incurable disease and the main cause of age-related dementia worldwide, despite decades of research. Treatment of AD with lithium (Li) has showed promising results, but the underlying mechanism is unclear. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. The plaques contain also metal ions of e.g. Cu, Fe, and Zn, and such ions are known to interact with Aβ peptides and modulate their aggregation and toxicity. The interactions between Aβ peptides and Li+ions have however not been well investigated. Here, we use a range of biophysical techniques to characterizein vitrointeractions between Aβ peptides and Li+ions. We show that Li+ions display weak and non-specific interactions with Aβ peptides, and have minor effects on Aβ aggregation. These results indicate that possible beneficial effects of Li on AD pathology are not likely caused by direct interactions between Aβ peptides and Li+ions.
High quality mapping of chromatin at or near the nuclear lamina for small numbers of cells
Authors: Tran Joseph R. , Zheng Xiaobin , Adam Stephen A. , Goldman Robert D. , Zheng Yixian 
Published: January 2021

AbstractThe chromatin associated with the nuclear lamina (NL) is referred to as Lamina-Associated Domains (LADs). While mapping of this feature has been done using various technologies, technical limitations exist for each of the methods. Here, we present an adaptation of the Tyramide-Signal Amplification sequencing (TSA-seq) protocol, which we call chromatin pull down-based TSA-seq (cTSA-seq), that can be used to map chromatin regions at or near the NL from as little as 50,000 cells without using carriers. The cTSA-seq mapped regions are composed of LADs and smaller chromatin regions that fall within the chromatin B-compartment known to be enriched for heterochromatin and be present at the nuclear periphery. As a proof of principle, we used cTSA-seq to map chromatin at or near the assembling NL as cells exit mitosis and progress through early and later G1. Consistent with previous reports, lamin-B1 based cTSA-seq revealed that regions toward the distal ends of chromosomes are near or at the reassembling NL during early G1. The cTSA-seq mapping and analyses revealed similarity between the early G1 chromatin and oncogene-induced senescent cell populations. The cTSA-seq reported here represents a useful method for analyzing chromatin at or near the NL from small numbers of cells.
Rab10-positive tubular structures represent a novel endocytic pathway that diverges from canonical macropinocytosis in RAW264 macrophages
Authors: Kawai Katsuhisa , Nishigaki Arata , Moriya Seiji , Egami Youhei , Araki Nobukazu 
Published: January 2021

AbstractUsing the optogenetic photo-manipulation of photoactivatable (PA)-Rac1, remarkable cell surface ruffling and the formation of a macropinocytic cup (premacropinosome) could be induced in the region of RAW264 macrophages irradiated with blue light due to the activation of PA-Rac1. However, the completion of macropinosome formation did not occur until Rac1 was deactivated by the removal of the light stimulus. Following PA-Rac1 deactivation, some premacropinosomes closed into intracellular macropinosomes, whereas many others transformed into long Rab10-positive tubules without forming typical macropinosomes. These Rab10-positive tubules moved centripetally towards the Golgi region along microtubules. Surprisingly, these Rab10-positive tubules did not contain any endosome/lysosome compartment markers, such as Rab5, Rab7, or LAMP1, suggesting that the Rab10-positive tubules were not part of the degradation pathway for lysosomes. These Rab10-positive tubules were distinct from recycling endosomal compartments, which are labeled with Rab4, Rab11, or SNX1. These findings suggested that these Rab10-positive tubules belonged to a novel, non-degradative, endocytic pathway. The formation of Rab10-positive tubules from premacropinosomes was also observed in control and phorbol myristate acetate (PMA)-stimulated macrophages, although their frequencies were low. Interestingly, the formation of Rab10-positive premacropinosomes and tubules was not inhibited by phosphoinositide 3-kinase (PI3K) inhibitors, while the classical macropinosome formation requires PI3K activity. Thus, this study provides evidence to support the existence of Rab10-positive tubules as a novel, non-degradative, endocytic pathway that diverges from canonical macropinocytosis.
Expectancy-Value-Cost motivational theory to explore final year medical students’ research intentions and past research experience: a multicentre cross-sectional questionnaire study
Authors: Van Maele Louis , Devos Christelle , Guisset Séverine , Leconte Sophie , Macq Jean 
Published: January 2021

ABSTRACTObjectivesConducting research during medical school is a commonly described way to strengthen the physician-scientists workforce. The aim of this study is to compare the strength of association of Expectancy, Value and Cost regarding a research activity with future research intentions, and to explore differences between students with or without research experience during medical school.Design, setting and participantsAn online questionnaire was sent to final-year medical students – who had already chosen their specialty – in three French-speaking Belgian universities with non-mandatory research programmes. Exploratory factor analysis (EFA) and multiple regression analysis were conducted.Main measuresResearch intention (outcome measure) was assessed using a 3-item scale. The motivational beliefs were assessed using a 10-item scale adapted from a validated scale based on the Expectancy-Value- Cost theory. Responses were recorded on a 6-point Likert scale.ResultsParticipation rate was 28% (n=237). EFA revealed 4 factors with high internal consistency. 21.5% of students had positive research intentions (score 5 or above). Our model explained 82.8% of research intention variance (p < 0.001), of which three motivational beliefs had statistically significant coefficients: i) Value given to a research activity (β = 0.72, p < 0.001); ii) perceived Cost of a research activity (β = -0.11, p < 0.01); iii) Expectancy of success (β = 0.10, p < 0.05). Students with a positive research experience or students without research experience but who had strongly considered achieving one were 11.5 times more likely (95% CI, 5.0 – 26.2) to have positive research intentions at the end of medical school than other students.ConclusionsValue given to a research activity is the key factor regarding students’ motivation to undertake research. Our study confirms the positive relationship between non-mandatory research and future research intentions, although some students without a research experience showed high motivation as well.
Do improved biomass cookstove interventions improve indoor air quality and blood pressure? A systematic review and meta-analysis
Authors: Kumar Nitya , Phillip Eunice , Cooper Helen , Davis Megan , Langevin Jessica , Clifford Mike , Stanistreet Debbi 
Published: January 2021

AbstractBackgroundHousehold air pollution (HAP) kills 4 million annually, with access to clean cooking being a challenge for 37% of the world’s population. Whilst there have been advancements in improved biomass cookstove (ICS) technologies, reviews on the impact of these ICS on HAP are now more than three years old.ObjectivesThis review and meta-analysis examines the most recent evidence on the impact of ICS on HAP and blood pressure (BP).MethodsA literature search was conducted using scientific literature databases and grey literature. Studies were included if they were published between January 2012 and June 2020, reported impact of ICS interventions in non-pregnant adults in low/middle-income countries, and reported post-intervention results along with baseline of traditional cookstoves. Outcomes included 24- or 48-hour averages of kitchen area fine particulate matter (PM2.5), carbon monoxide (CO), mean systolic BP (SBP) and mean diastolic BP (DBP). Meta-analyses estimated weighted mean differences between baseline and post-intervention values for all outcome measures.ResultsNine studies were included; eight contributed estimates for HAP and three for BP. Interventions lead to significant reductions in PM2.5 (−0.28 mg/m3, 95% CI: -0.46, -0.10), CO (−6.59ppm, 95%CI: - 10.73, -2.46) and SBP (−2.82mmHg, 95% CI: -5.53, -0.11); and a non-significant reduction in DBP (−0.80 mmHg, 95%CI: -2.33, 0.73), when compared to baseline of traditional cookstoves. Except for DBP, greatest reductions in all outcomes came from standard combustion ICS with a chimney, compared to ICS without a chimney and advanced combustion ICS. WHO air quality targets were met by post-intervention values for CO but not for PM2.5.ConclusionOur review suggests that ICS with a chimney results in the greatest reductions in HAP and BP. Further research on qualitative impact of such ICS on end-users is required to understand feasibility of adoption at scale.
T cell Homeostatic Imbalance in Placentae from Women with HIV in the absence of Vertical Transmission
Authors: Ikumi Nadia M. , Pillay Komala , Tilburgs Tamara , Malaba Thokozile R. , Dzanibe Sonwabile , Ann L Enninga Elizabeth , Chakraborty Rana , Lamorde Mohammed , Myer Landon , Khoo Saye , Jaspan Heather B , Gray Clive M. ,   for the DolPHIN-2 Study Group
Published: January 2021

ABSTRACTBackgroundImplementation of universal antiretroviral therapy (ART) has significantly lowered vertical transmission rates but has also increased numbers of HIV-exposed uninfected children (HEU), who remain vulnerable to morbidities. Here, we investigated whether T cell alterations in the placenta contribute to altered immune status in HEU.MethodsWe analyzed T cells from term placentae decidua and villous tissue and paired cord blood from pregnant women with HIV (PWH) who initiated ART late in pregnancy (n=21) with pregnant women not living with HIV (PWNH) (n=9).ResultsPlacentae from PWH showed inverted CD4:CD8 ratios and higher proportions of tissue resident CD8+ T cells in villous tissue relative to control placentae. CD8+ T cells in the fetal capillaries, which were of fetal origin, positively correlated with maternal plasma viraemia prior to ART initiation, implying that imbalanced T cells persisted throughout pregnancy. Additionally, the expanded memory differentiation of CD8+ T cells was confined to the fetal placental compartment and cord blood but was not observed in the maternal decidua.ConclusionsT cell homeostatic imbalance in the blood circulation of PWH is reflected in the placenta. The placenta may be a causal link between HIV-induced maternal immune changes during gestation and altered immunity in newborn infants in the absence of vertical transmission.Lay SummaryThe effective prevention of HIV transmission during pregnancy with the rollout of antiretroviral therapy (ART) has resulted in increased numbers of HIV-exposed uninfected children (HEU). These children are vulnerable to infections and health problems and have distorted cellular immune systems at birth. We investigated whether these immune alterations originate in the placenta, as this fetal organ maintains life during pregnancy. After collecting placentae at term from pregnant women living with HIV (PWH), who started ART in the third trimester (n=21) and from pregnant women not living with HIV (PWNH) (n=9), we isolated T cells from dissected placental tissue and matching cord blood. Placentae from PWH showed inverted CD4:CD8 ratios in the placenta and cord blood with higher numbers of CD8+ T cells in the fetal part of the placenta. These CD8+ T cells mirrored events in the blood circulation of the mother and the altered balance of T cell immunity in the PWH was reflected in the placenta. Accordingly, the placenta may be a pivotal link between HIV-induced maternal immune changes and altered immunity in newborn infants in the absence of vertical transmission.
Locomotion-induced ocular motor behavior in larvalXenopusis developmentally tuned by visuo-vestibular reflexes
Authors: Bacqué-Cazenave Julien , Courtand Gilles , Beraneck Mathieu , Straka Hans , Combes Denis , Lambert François M. 
Published: January 2021

ABSTRACTLocomotion requires neural computations to maintain stable perception of the world despite disturbing consequences of the motor behavior on sensory stability. The developmental establishment of locomotor proficiency is therefore accompanied by a concurrent maturation of gaze-stabilizing motor behaviors. Using developing larvalXenopus, we demonstrate mutual plasticity of predictive spinal locomotor efference copies and multi-sensory motion signals with the aim to constantly ensure dynamically adequate eye movements during swimming. Following simultaneous ontogenetic onsets of locomotion, spino-ocular, optokinetic and otolith-ocular motor behaviors, locomotor efference copy-driven eye movements improve through gradually augmenting influences of semicircular canal signals. Accordingly, neuronal computations change from a predominating cancelation of angular vestibulo-ocular reflexes by locomotor efference copies in young larvae to a summation of these signals in older larvae. The developmental switch occurs in synchrony with a reduced efficacy of the tail-undulatory locomotor pattern generator causing gradually decaying influences on the ocular motor output.
FAM134B-RHD Protein Clustering Drives Spontaneous Budding of Asymmetric Membranes
Authors: Siggel Marc , Bhaskara Ramachandra M. , Moesser Melanie K. , Đikić Ivan , Hummer Gerhard 
Published: January 2021

AbstractLiving cells constantly remodel the shape of their lipid membranes. In the endo-plasmic reticulum (ER), the reticulon homology domain (RHD) of the reticulophagy regulator 1 (RETR1/FAM134B) forms dense autophagic puncta that are associated with membrane removal by ER-phagy. In molecular dynamics (MD) simulations, we find that FAM134B-RHD spontaneously forms clusters, driven in part by curvature-mediated attraction. At a critical size, the FAM134B-RHD clusters induce the formation of membrane buds. The kinetics of budding depends sensitively on protein concentration and bilayer asymmetry. Our MD simulations shed light on the role of FAM134B-RHD in ER-phagy and show that membrane asymmetry can be used to modulate the kinetics barrier for membrane remodeling.Graphical TOC Entry
Effects of chronic lithium treatment on anxious behaviors and serotonergic genes expression in the midbrain raphe nuclei in defeated male mice
Authors: Smagin Dmitry A. , Kovalenko Irina L. , Galyamina Anna G. , Belozertseva Irina V. , Tamkovich Nikolay V. , Baranov Konstantin O. , Kudryavtseva Natalia N. 
Published: January 2021

AbstractThere are experimental data that mixed anxiety/depression-like state induced by chronic social defeat stress is accompanied by development of anxiety and downregulation of serotonergic gene expression in the midbrain raphe nuclei of male mice. The paper aimed to study the effect of chronic lithium chloride (LiCl) on anxious behaviors and the expression of serotonergic genes (Tph2,Slc6a4,Htr1a,Htr5b) in the midbrain raphe nuclei of defeated mice. Slight anxiolytic effects of LiCl were found on the commucativeness in the partition test, and anxiogenic-like effects, estimated by the elevated plus-maze and social interactions tests. Chronic LiCl treatment induced overexpression of the serotonergic genes in the midbrain raphe nuclei of defeated mice. We can assume that effects of LiCl, rather anxiogenic, may be due to activation of serotonergic system induced by hyperexpression of serotonergic genes. Our findings will allow to understand the factors involved in the positive and side effects of lithium on anxiety and function of serotonergic genes which are involved into mechanisms of depression.
pr2-primers: an 18S rRNA primer database for protists
Authors: Vaulot Daniel , Geisen Stefan , Mahé Frédéric , Bass David 
Published: January 2021

AbstractMetabarcoding of microbial eukaryotes (collectively known asprotists) has developed tremendously in the last decade, almost uniquely relying on the 18S rRNA gene. As microbial eukaryotes are extremely diverse, many primers and primer pairs have been developed. To cover a relevant and representative fraction of the protist community in a given study system, a wise primer choice is needed as no primer pair can target all protists equally well. As such, a smart primer choice is very difficult even for experts and there are very few on-line resources available to list existing primers. We built a database listing 179 primers and 76 primer pairs that have been used for eukaryotic 18S rRNA metabarcoding.In silicoperformance of primer pairs was tested against two sequence databases: PR2for eukaryotes and a subset of Silva for prokaryotes. This allowed to determine the taxonomic specificity of primer pairs, the location of mismatches as well as amplicon size. We developed a R-based web application that allows to browse the database, visualize the taxonomic distribution of the amplified sequences with the number of mismatches, and to test any user-defined primer set (https://app.pr2-primers.org). This tool will provide the basis for guided primer choices that will help a wide range of ecologists to implement protists as part of their investigations.
Microsecond resolved infrared spectroscopy on non-repetitive protein reactions by applying caged-compounds and quantum cascade laser frequency combs
Authors: Norahan Mohamad Javad , Horvath Raphael , Woitzik Nathalie , Jouy Pierre , Eigenmann Florian , Gerwert Klaus , Kötting Carsten 
Published: January 2021

ABSTRACTInfrared spectroscopy is ideally suited for the investigation of protein reactions at the atomic level. Many systems were investigated successfully by applying Fourier transform infrared (FTIR) spectroscopy. While rapid-scan FTIR spectroscopy is limited by time resolution (about10 ms with 16 cm-1resolution), step-scan FTIR spectroscopy reaches a time-resolution of about 10 ns but is limited to cyclic reactions that can be repeated hundreds of times under identical conditions. Consequently, FTIR with high time resolution was only possible with photoactivable proteins that undergo a photocycle. The huge number of non-repetitive reactions, e.g. induced by caged compounds, were limited to the ms time domain. The advent of dual comb quantum cascade laser allows now for a rapid reaction monitoring in the μs time domain. Here we investigate the potential to apply such an instrument to the huge class of G-proteins. We compare caged-compound induced reactions monitored by FTIR and dual comb spectroscopy, respectively, by applying the new technique to the α subunit of the inhibiting Giprotein and to the larger protein-protein complex of Gαiwith its cognate regulator of G-protein signaling (RGS). We observe good data quality with 4 μs time resolution with a wavelength resolution comparable to FTIR. This is more than three orders of magnitude faster than any FTIR measurement on G-proteins in the literature. This study paves the way for infrared spectroscopic studies in the so far unresolvable μs time regime for non-repetitive biological systems including all GTPases and ATPases.
Photosynthetic acclimation and sensitivity to short- and long-term environmental changes
Authors: Schönbeck Leonie , Grossiord Charlotte , Gessler Arthur , Gisler Jonas , Meusburger Katrin , D’Odorico Petra , Rigling Andreas , Salmon Yann , Stocker Benjamin D. , Zweifel Roman , Schaub Marcus 
Published: January 2021

SummaryThe future climate will be characterized by an increase in frequency and duration of drought and warming that exacerbates atmospheric evaporative demand. How trees acclimate to long-term soil moisture changes and whether these long-term changes alter trees’ sensitivity to short-term (day to months) variations of vapor pressure deficit (VPD) and soil moisture is largely unknown.Leaf gas exchange measurements were performed within a long-term (17 years) irrigation experiment in a Scots pine-dominated forest in one of Switzerland’s driest areas on trees in naturally dry (control), irrigated, and‘irrigation-stop’ (after 11 years of irrigation) conditions.Seventeen years of irrigation increased photosynthesis (A) and stomatal conductance (gs) and reduced the gssensitivity to increasing VPD but not to soil drying. Following irrigation-stop, gas exchange did not decrease immediately, but after three years, had decreased significantly in irrigation-stop trees. Vcmaxand Jmaxrecovered after five years.These results suggest that long-term release of soil drought reduces the sensitivity to atmospheric evaporative demand and that atmospheric constraints may play an increasingly important role in combination with soil drought. In addition, they suggest that structural adjustments lead to an attenuation of initially strong leaf-level acclimation to strong multiple-year drought.
scRNA-seq Reveals A Macrophage Subset That Provides A Splenic Replication Niche For IntracellularSalmonella
Authors: Hoffman Dotan , Tevet Yaara , Rosenberg Gili , Vainman Leia , Solomon Aryeh , Hen-Avivi Shelly , Ben-Moshe Noa Bossel , Avraham Roi 
Published: January 2021

AbstractInteractions between intracellular bacteria and mononuclear phagocytes give rise to diverse cellular phenotypes that may determine the outcome of infection. Recent advances in single cell RNA-seq (scRNA-seq) have identified multiple subsets within the mononuclear population defined by unique molecular features, but the implications to their function during infection is unknown. Here, we applied high resolution kinetic analysis using microscopy, flow cytometry and scRNA-seq to survey the mononuclear niche of intracellularSalmonellaTyphimurium (S.Tm) during early systemic infection in mice. We describe an eclipse like growth kinetics in the spleen, with a first phase of bacterial control mediated by tissue resident red pulp macrophages. A second phase involved bacterial growth mediated by intracellular replication within a macrophage population we termed CD9 macrophages, that originate from non-classical monocytes.Nr4a1e2−/−mice, specifically depleted of non-classical monocytes but not other mononuclear cells, are more resistant toS.Tm infection. Our study underscores a cell-type specific host-pathogen interaction that determines early infection growth dynamics and has implications to the infection outcome of the entire organism.