bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigating the psychological impacts of COVID-19 restrictions: The Behavioural Activation in Social Isolation (BASIL) pilot randomised controlled trial to prevent depression and loneliness among older people with long term conditions
Authors: Gilbody Simon , Littlewood Elizabeth , McMillan Dean , Chew-Graham Carolyn A. , Bailey Della , Gascoyne Samantha , Sloan Claire , Burke Lauren , Coventry Peter , Crosland Suzanne , Fairhurst Caroline , Henry Andrew , Hewitt Catherine , Joshi Kalpita , Ryde Eloise , Shearsmith Leanne , Traviss-Turner Gemma , Woodhouse Rebecca , Clegg Andrew , Gentry Tom , Hill Andrew , Lovell Karina , Smith Sarah Dexter , Webster Judith , Ekers David 
Published: May 2021

AbstractBackgroundOlder adults with long-term conditions have become more socially isolated (often due to advice to ‘shield’ to protect them from COVID-19) and are thus at particular risk of depression and loneliness. There is a need for brief scalable psychosocial interventions to mitigate the psychological impacts of social isolation. Behavioural Activation is a plausible intervention, but a trial is needed.MethodsWe undertook an external randomised pilot trial (ISRCTN94091479) designed to test recruitment, retention and engagement with, and the acceptability and preliminary effects of the intervention. Participants aged ≥ 65 years with two or more long-term conditions were recruited between June and October 2020. Behavioural Activation was offered to intervention participants (n=47), and control participants received usual care (n=49).FindingsRemote recruitment was possible and 45/47 (95.7%) randomised to the intervention completed one or more sessions (median 6 sessions). 90 (93.8%) completed the one month follow-up, and 86 (89.6%) completed the three month follow-up. The between-group comparison for the primary clinical outcome at one month was an adjusted between group mean difference of −0.50 PHQ-9 points (95% CI −2.01 to 1.01), but only a small number of participants had completed the intervention at this point. At three months, the PHQ-9 adjusted mean difference was 0.19 (95% CI −1.36 to 1.75). When we examined loneliness, the between-group difference in the De Jong Gierveld Loneliness scale at one month was 0.28 (95% CI −0.51 to 1.06), and there was statistically significant between group difference at three months (−0.87; 95% CI −1.56 to −0.18). Participants who withdrew had minimal depressive symptoms at entry.InterpretationBehavioural Activation is a plausible intervention to mitigate the psychological impacts of COVID-19 isolation for older adults. The intervention can be delivered remotely and at scale, but should be reserved for older adults with evidence of depressive symptoms. The significant reduction in loneliness is unlikely to be a chance finding, and this will now be confirmed in a fully powered RCT.FundingThis study was funded by National Institute for Health Research (NIHR) Programme Grants for Applied Research (PGfAR) RP-PG-0217-20006
Deceleration of cell cycle underpins a switch from proliferative- to terminal division in plant stomatal lineage
Authors: Han Soon-Ki , Yang Jiyuan , Arakawa Machiko , Iwasaki Rie , Sakamoto Tomoaki , Kimura Seisuke , Kim Eun-Deok , Torii Keiko U. 
Published: May 2021

ABSTRACTDifferentiation of specialized cell types from self-renewing progenitors requires precise cell cycle control. Plant stomata are generated through asymmetric divisions of a stem-cell-like precursor meristemoid followed by the single symmetric division that creates an adjustable pore surrounded by paired guard cells. The stomatal-lineage-specific transcription factor MUTE terminates the asymmetric divisions and triggers differentiation. However, the role of cell cycle machinery in this transition remains unknown. Through time-lapse imaging, we discover that the symmetric division is slower than the asymmetric division. We identify a plant-specific cyclin-dependent kinase inhibitor, SIAMESE-RELATED4 (SMR4), as a molecular brake that decelerates cell cycle during this transition. SMR4 is directly induced by MUTE and transiently accumulates in differentiating meristemoids. SMR4 physically and functionally associates with CYCD3;1 and extends G1-phase of asymmetric divisions. By contrast, SMR4 fails to interact with CYCD5;1, a MUTE-induced G1 cyclin, and permits the symmetric division. Our work unravels a molecular framework of the proliferation-to-differentiation switch within the stomatal lineage and suggests that a timely proliferative cell cycle is critical for the stomatal fate specification.
Development of a Low-Cost System for Simultaneous Longitudinal Biological Imaging
Authors: Ly Victoria T. , Baudin Pierre V. , Pansodtee Pattawong , Jung Erik A. , Voitiuk Kateryna , Rosen Yohei M. , Willsey Helen Rankin , Mantalas Gary L. , Seiler Spencer T. , Selberg John A. , Cordero Sergio A. , Ross Jayden M. , Rolandi Marco , Pollen Alex A. , Nowakowski Tomasz J. , Haussler David , Mostajo-Radji Mohammed A. , Salama Sofie R. , Teodorescu Mircea 
Published: May 2021

ABSTRACTSimultaneous longitudinal imaging across multiple conditions and replicates has been crucial for scientific studies aiming to understand biological processes and disease. Yet, imaging systems capable of accomplishing these tasks are economically unattainable for most academic and teaching laboratories around the world. Here we propose the Picroscope, which is the first low cost system for simultaneous longitudinal biological imaging made primarily using off-the-shelf and 3D-printed materials. The Picroscope is compatible with standard 24-well cell culture plates and captures 3D z-stack image data. The Picroscope can be controlled remotely, allowing for automatic imaging with minimal intervention from the investigator. Here we use this system in a range of applications. We gathered longitudinal whole organism image data for frogs, zebrafish and planaria worms. We also gathered image data inside an incubator to observe 2D monolayers and 3D mammalian tissue culture models. Using this tool, we can measure the behavior of entire organisms or individual cells over long time periods.
A quantitative map of nuclear pore assembly reveals two distinct mechanisms
Authors: Otsuka Shotaro , Tempkin Jeremy O. B. , Zhang Wanlu , Politi Antonio Z. , Rybina Arina , Hossain M. Julius , Kueblbeck Moritz , Callegari Andrea , Koch Birgit , Morero Natalia Rosalia , Sali Andrej , Ellenberg Jan 
Published: May 2021

SummaryUnderstanding how the nuclear pore complex (NPC) assembles is of fundamental importance to grasp the mechanisms behind its essential function and understand its role during evolution of eukaryotes1–4. While at least two NPC assembly pathways exist, one during exit from mitosis and one during nuclear growth in interphase, we currently lack a quantitative map of the molecular assembly events. Here, we use fluorescence correlation spectroscopy (FCS) calibrated live imaging of endogenously fluorescently-tagged nucleoporins to map the changes in composition and stoichiometry of seven major modules of the human NPC during its assembly in single dividing cells. This systematic quantitative map reveals that the two assembly pathways employ strikingly different molecular mechanisms, inverting the order of addition of two large structural components, the central ring complex and nuclear filaments. The dynamic stoichiometry data underpinned integrative spatiotemporal modeling of the NPC assembly pathway, predicting the structures of postmitotic NPC assembly intermediates.
Drug-induced colorectal cancer persister cells show increased mutation rate
Authors: Russo Mariangela , Pompei Simone , Sogari Alberto , Corigliano Mattia , Crisafulli Giovanni , Bertotti Andrea , Gherardi Marco , Di Nicolantonio Federica , Bardelli Alberto , Lagomarsino Marco Cosentino 
Published: May 2021

AbstractCompelling evidence shows that cancer persister cells limit the efficacy of targeted therapies. However, it is unclear whether persister cells are induced by anticancer drugs, and if their mutation rate quantitatively increases during treatment. Here, combining experimental characterization and mathematical modeling, we show that, in colorectal cancer, persisters are induced by drug treatment and show a 7- to 50-fold increase of mutation rate when exposed to clinically approved targeted therapies. These findings reveal that treatment may influence persistence and mutability in cancer cells and pinpoints new strategies to restrict tumor recurrence.
New strategy to select cross-reactivity Meningococci strains: immunization with Outer membrane vesicles of serogroup C and cationic lipid as adjuvant
Authors: Portilho Amanda Izeli , de Lima Gabriela Trzewikowski , De Gaspari Elizabeth 
Published: May 2021

AbstractBackgroundInvasive meningococcal disease (IMD), caused by Neisseria meningitidis, is a public health problem, associated with high levels of morbidity and mortality, capable of causing outbreaks or epidemics, but preventable through vaccination. In Brazil, the main serogroups isolated are C and B. The last epidemic occurred in the ‘80s, in São Paulo, because of a B:4:P1.15 strain.MethodsAdult Swiss mice were immunized with outer membrane vesicles (OMV) of N. meningitidis strain C:4:P1.15, adjuvanted by the cationic lipid dioctadecyldimethylammonium bromide in bilayer fragments (DDA-BF), administered via prime-booster (intranasal/subcutaneous) scheme. The humoral response was accessed by Immunoblotting and ELISA, using homologous immunization strain and a different serogroup but equal serosubtype strain, N. meningitidis B:4:P1.15.ResultsImmunoblotting revealed the recognition of antigens associated with the molecular weight of Porin A and Opacity proteins, which are immunogenic but highly heterogeneous, and Tbp and NspA, which are more homogeneous between meningococci strains. ELISA results showed antibody production that persisted after 190 days and recognized the C:4:P1.15 and the B:4:P1.15 strains, with high avidity index. The adjuvanted group recognized antigens following the IN prime and had a higher avidity index against the heterologous strain.ConclusionsDDA-BF improved the humoral response, but the OMV alone induced high avidity index antibodies as well. Even though these are preliminary results, we see it as a promising approach for affordable meningococcal immunization in developing countries, at outbreak or epidemic situations.
Modeling the stepwise extension of recombination suppression on sex chromosomes and other supergenes through deleterious mutation sheltering
Authors: Jay Paul , Tezenas Emilie , Véber Amandine , Giraud Tatiana 
Published: May 2021

AbstractMany organisms have sex chromosomes with large non-recombining regions that have expanded stepwise, generating “evolutionary strata” of differentiation. The reasons for this remain poorly understood, but the principal hypotheses proposed to date are based on antagonistic selection due to differences between sexes. However, it has proved difficult to obtain empirical evidence of a role for sexually antagonistic selection in extending recombination suppression, and antagonistic selection has been shown to be unlikely to account for the evolutionary strata observed on fungal mating-type chromosomes. There may, therefore, be other mechanisms involved in the extension of non-recombining regions. We show here, by mathematical modeling and stochastic simulation, that recombination suppression on sex chromosomes and around supergenes can expand in a stepwise manner under a wide range of parameter values simply because it shelters recessive deleterious mutations, which are ubiquitous in genomes. Permanently heterozygous alleles, such as the maledetermining allele in XY systems, protect linked chromosomal inversions against the expression of their recessive mutation load, leading to the successive accumulation of inversions around these alleles without the need for antagonistic selection. Similar results were obtained with models assuming recombination-suppressing mechanisms other than chromosomal inversions, and for supergenes other than sex chromosomes, including those without XY-like asymmetry, such as fungal mating-type chromosomes. However, inversions capturing a permanently heterozygous allele were found to be less likely to spread when the mutation load was lower (e.g. under conditions of large effective population size, low mutation rates and high dominance coefficients). This may explain why sex chromosomes remain homomorphic in some organisms but are highly divergent in others. Here, we explicitly state and model a simple and testable hypothesis explaining the existence of stepwise extensions of recombination suppression on sex chromosomes, which can also be applied to mating-type chromosomes and supergenes in general.
Synaptic Plasticity in the Agranular Insular Cortex Predicts Escalated Ethanol Consumption
Authors: Shillinglaw Joel E. , Aziz Heather C. , Carrizales Daniela G. , Morrisett Richard A. , Mangieri Regina A. 
Published: May 2021

AbstractThe Agranular Insular Cortex (AIC) is implicated in alcohol use disorder and pharmacologically relevant concentrations of acute ethanol inhibit N-methyl-D-aspartate receptor (NMDAR)-mediated glutamatergic synaptic transmission and plasticity onto layer 2/3 AIC pyramidal neurons. However, it is not known whether the actions of ethanol on glutamatergic synapses are means by which chronic ethanol alters mechanisms of learning and memory in AIC as alcohol drinking transitions from controlled to problematic. We utilized the chronic intermittent ethanol (CIE) vapor model of ethanol exposure in adult male mice, alone or in combination with voluntary ethanol consumption, to determine whether glutamatergic synapses on layer 2/3 AIC pyramidal neurons are differentially regulated by different durations and intensities of chronic ethanol exposure. We observed evidence of both ethanol- and age-related metaplasticity of AIC layer 2/3 glutamatergic synapses, as only young adult, ethanol-naïve mice exhibited NMDAR-dependent long term depression ex vivo. Our findings also indicated that voluntary ethanol consumption alone can elicit glutamatergic plasticity in vivo. We found that the ratio of NMDAR- to AMPAR-mediated postsynaptic currents was reduced not only in CIE-treated, but also in air-treated, chronically drinking mice relative to ethanol-naïve controls. Furthermore, lower NMDA/AMPA ratios were predictive of greater escalation of ethanol consumption. These findings suggest that even moderate exposure to ethanol may elicit plasticity in the agranular insular cortex that contributes to the progression toward uncontrolled drinking.
Nicotinic acetylcholine receptor partial antagonist polyamides from tunicates and their predatory sea slugs
Authors: Paguigan Noemi D. , Tun Jortan O. , Leavitt Lee S. , Lin Zhenjian , Chase Kevin , Dowell Cheryl , Deering-Rice Cassandra E. , Lim Albebson L. , Karthikeyan Manju , Hughen Ronald W. , Zhang Jie , Peterson Randall T. , Reilly Christopher A. , Light Alan R. , Raghuraman Shrinivasan , McIntosh J. Michael , Olivera Baldomero M. , Schmidt Eric W. 
Published: May 2021

ABSTRACTIn our efforts to discover new drugs to treat pain, we identified molleamines A-E (1-5) as major neuroactive components of the sea slug, Pleurobranchus forskalii and their prey, Didemnum molle tunicates. The chemical structures of molleamines were elucidated by spectroscopy and confirmed by the total synthesis of molleamines A (1) and C (3). Synthetic 3 completely blocked acetylcholine-induced calcium flux in peptidergic nociceptors (PNs) in the somatosensory nervous system. Compound 3 affected neither the α7 nAChR nor the muscarinic acetylcholine receptors in calcium flux assays. In addition to nociceptors, 3 partially blocked the acetylcholine-induced calcium flux in the sympathetic nervous system, including neurons from the superior cervical ganglion. Electrophysiology revealed a block of α3β4 (mouse) and α6/α3β4 (rat) nicotinic acetylcholine receptors (nAChRs), with IC50 values of 1.4 and 3.1 µM, respectively. Molleamine C (3) is a partial antagonist, reaching a maximum block of 76-82% of the acetylcholine signal and showing no partial agonist response. Molleamine C (3) may thus provide a lead compound for the development of neuroactive compounds with unique biological properties.
Basal Ganglia Responses to Electrical Stimulation of the Posterior Hypothalamic Nucleus
Authors: Young Calvin K. , Bland Brian H. 
Published: May 2021

AbstractElectrical or chemical stimulation of the posterior hypothalamic nucleus (PH) elicits highly adaptive locomotion, demonstrating both evidence of flexibility and variety in exhibited motor behaviours. However, the neural substrates of PH stimulation elicited behavioural changes are poorly understood. The basal ganglia are postulated to be critically involved in the process of action selection in conjunction with thalamo-cortical systems. The present study examines changes in basal ganglia activities in response to the high-frequency stimulation of the PH. Under urethane anaesthesia, ensemble and single-unit recordings were obtained from the striatum (STR), globus pallidus externa (GPe), entopeduncular nucleus (EP), subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr). Upon PH stimulation, increases in firing rates were observed in the STR, GPe, and STN, a decrease was observed in the SNr and no changes were seen in the EP. The increase in spike rate in the STR and GPe was dependent on the stimulation intensity but not duration. Despite the differences in the direction of firing changes during PH stimulation, all examined areas including those not part of the basal ganglia demonstrated an elevated spiking rate upon stimulus train termination. Taking into account the known anatomical connections between the PH and the basal ganglia, it is hypothesized responses seen during PH stimulus trains are mediated through thalamic and cortical relays whereas the overall post-stimulus excitatory response is related to the impact of the PH on brainstem arousal systems.
Polarized Dishevelled dissolution and condensation drives embryonic axis specification in oocytes
Authors: Swartz S. Zachary , Tan Tzer Han , Perillo Margherita , Fakhri Nikta , Wessel Gary M. , Wikramanayake Athula H. , Cheeseman Iain M. 
Published: May 2021

SUMMARYThe organismal body axes that are formed during embryogenesis are intimately linked to intrinsic asymmetries established at the cellular scale in oocytes [1]. Here, we report an axis-defining event in meiotic oocytes of the sea star Patiria miniata. Dishevelled is a cytoplasmic Wnt pathway effector required for axis development in diverse species [2-4], but the mechanisms governing its function and distribution remain poorly defined. Using time-lapse imaging, we find that Dishevelled localizes uniformly to puncta throughout the cell cortex in Prophase I-arrested oocytes, but becomes enriched at the vegetal pole following meiotic resumption through a dissolution-condensation mechanism. This process is driven by an initial disassembly phase of Dvl puncta, followed by selective reformation of Dvl assemblies at the vegetal pole. Rather than being driven by Wnt signaling, this localization behavior is coupled to meiotic cell cycle progression and influenced by Lamp1+ endosome association and Frizzled receptors pre-localized within the oocyte cortex. Our results reveal a cell cycle-linked mechanism by which maternal cellular polarity is transduced to the embryo through spatially-regulated Dishevelled dynamics.
Differential surface competition and biofilm invasion strategies of Pseudomonas aeruginosa PA14 and PA01
Authors: Katharios-Lanwermeyer Stefan , Kassety Swetha , Nadell Carey D. , O’Toole George A. 
Published: May 2021

AbstractPseudomonas aeruginosa strains PA14 and PAO1 are among the two best characterized model organisms used to study the mechanisms of biofilm formation, while also representing two distinct lineages of P. aeruginosa. Our previous work showed that P. aeruginosa PA14 and PAO1 use distinct strategies to initiate biofilm growth. Using differentially-labeled strains and microfluidic devices, we show that PAO1 can outcompete PA14 in a head-to-head competition during early colonization of a surface, can do so in constant and perturbed environments, that this advantage is specific to biofilm growth and requires production of the Psl polysaccharide. In contrast, the P. aeruginosa PA14 exhibits a competitive fitness advantage when invading a pre-formed biofilm and is better able to tolerate starvation than PAO1 in the biofilm context. These data support the model that while P. aeruginosa PAO1 and PA14 are both able to effectively colonize surfaces, these strains use distinct strategies that are advantageous under different environmental settings.ImportanceRecent studies indicate that P. aeruginosa PAO1 and PA14 use distinct strategies to initiate biofilm formation, with PAO1 committing to the surface through a processive mode of attachment, while PA14 uses a non-processive surface engagement strategy. We investigated whether their respective colonization strategies impact their ability to effectively compete under different biofilm-forming regimes. Our work shows that these different strategies do indeed impact how these strains colonize the surface: PAO1 dominates during colonization of a naïve surface, while PA14 is more effective in colonizing a pre-formed biofilm or withstanding starvation conditions. These data suggest that even for very similar microbes there may be distinct strategies to successfully colonize and persist on surfaces during the biofilm life cycle.
Biochemical Barriers on the Path to Ocean Anoxia?
Authors: Giovannoni Stephen , Chan Francis , Davis Edward , Deutsch Curtis , Wolf Sarah 
Published: May 2021

ABSTRACTThe kinetics of microbial respiration suggest that, if excess organic matter is present, oxygen should fall to nanomolar levels, in the range of the Michaelis-Menten constants (Km). Yet even in many biologically productive coastal regions, lowest observed O2 concentrations often remain several orders of magnitude higher than respiratory Km values. We propose the Hypoxic Barrier Hypothesis (HBH) to explain this apparent discrepancy. The HBH postulates that oxidative enzymes involved in organic matter catabolism are kinetically limited by O2 at concentrations far higher than the thresholds for respiration. We found support for the HBH in a meta-analysis of 1137 O2 Km values reported in the literature: the median value for terminal respiratory oxidases was 350 nM, but for other oxidase types the median value was 67 μM. The HBH directs our attention to the kinetic properties of an important class of oxygen-dependent reactions that could help explain the trajectories of ocean ecosystems experiencing O2 stress.IMPORTANCEDeclining ocean oxygen associated with global warming and climate change is impacting marine ecosystems across scales from microscopic planktonic communities to global fisheries. We report a fundamental dichotomy in the affinity of enzymes for oxygen. The importance of this observation has yet to be fully assessed, but it is predicted to impact the rate at which organic matter is oxidized in hypoxic ecosystems, and the types of organic matter that accumulate. Competition between intracellular enzymes for oxygen may also have impacted microbial strategies of adaptation to suboxia.