bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal effects of using and discontinuing CNS medications on cognitive functioning
Authors: Koch Elise , Johnell Kristina , Kauppi Karolina 
Published: September 2021

AbstractPurposeTo investigate the longitudinal effect of using and discontinuing central nervous system (CNS) medications on cognitive performance.MethodsUsing longitudinal cognitive data from healthy adults aged 25-100 years (N = 2,188) from four test waves five years apart, we investigated both the link between use of CNS medications (opioids, antidepressants, and anxiolytics, hypnotics and sedatives) on cognitive task performance (episodic memory, semantic memory, visuospatial ability) across 15 years, and the effect of discontinuing these medications in linear mixed effects models.ResultsWe found that opioid use was associated with decline in visuospatial ability, whereas antidepressant use was associated with decline in semantic memory over 15 years. A link between drug discontinuation and cognitive improvement was seen for opioids, antidepressants as well as for anxiolytics, hypnotics and sedatives.ConclusionsAlthough our results may be confounded by subjacent conditions, they suggest that long-term use of CNS medications may have domain-specific negative effects on cognitive performance over time, whereas the discontinuation of these medications may partly reverse these effects. These results open up for future studies that address subjacent conditions on cognition to develop a more complete understanding of the cognitive effects of CNS medications.Key pointsOpioid use was associated with decline in visuospatial ability, and individuals discontinuing using opioids showed improvement in visuospatial ability compared to individuals continuing using opioids.Antidepressant use was associated with decline in semantic memory, and individuals discontinuing using antidepressants showed improvement in semantic memory compared to individuals continuing using antidepressants.For anxiolytics, hypnotics and sedatives there was no difference between continued users and non-users, but drug discontinuation was associated with more positive cognitive development both in episodic memory and visuospatial ability.
Structural Disconnection of the Posterior Medial Frontal Cortex Reduces Speech Error Monitoring
Authors: McCall Joshua D. , Dickens J. Vivian , Mandal Ayan S. , DeMarco Andrew T. , Fama Mackenzie E. , Lacey Elizabeth H. , Kelkar Apoorva , Medaglia John D. , Turkeltaub Peter E. 
Published: September 2021

ABSTRACTOptimal performance in any task relies on the ability to detect and repair errors. The anterior cingulate cortex and the broader posterior medial frontal cortex (pMFC) are active during error processing. However, it is unclear whether damage to the pMFC impairs error monitoring. We hypothesized that successful error monitoring critically relies on connections between the pMFC and broader cortical networks involved in executive functions and the task being monitored. We tested this hypothesis in the context of speech error monitoring in people with post-stroke aphasia. Diffusion weighted images were collected in 51 adults with chronic left-hemisphere stroke and 37 age-matched control participants. Whole-brain connectomes were derived using constrained spherical deconvolution and anatomically-constrained probabilistic tractography. Support vector regressions identified white matter connections in which lost integrity in stroke survivors related to reduced error detection during confrontation naming. Lesioned connections to the bilateral pMFC were related to reduce error monitoring, including many connections to regions associated with speech production and executive function. We conclude that connections to the pMFC support error monitoring. Error monitoring in speech production is supported by the structural connectivity between the pMFC and regions involved in speech production and executive function. Interactions between pMFC and other taskrelevant processors may similarly be critical for error monitoring in other task contexts.
Orientation dependent proton transverse relaxation in the human brain white matter: The magic angle effect on a cylindrical helix
Authors: Pang Yuxi 
Published: September 2021

ABSTRACTPurposeTo overcome some limitations of prior orientation-dependent proton transverse relaxation formalisms in white matter (WM) with a novel framework based on the generalized magic angle effect function.MethodsA cylindrical helix model was developed embracing anisotropic rotational and translational diffusion of restricted molecules in human brain WM, with the former characterized by an axially symmetric system. Transverse relaxation ratesR2andwere divided into isotropicand anisotropic parts,, withαdenoting an open angle andε0an orientation (Φ) offset from DTI-derived primary diffusivity direction. The proposed framework (Fit A) was compared with prior models withoutε0on previously published water and methylene proton transverse relaxation rates from developing, healthy, and pathological WM at 3T. Goodness of fit was represented by root-mean-square error (RMSE).F-test and linear correlation were used with statistical significance set toP≤ 0.05.ResultsFit A significantly (P<0.01) outperformed prior models as demonstrated by reduced RMSEs, e.g., 0.349 vs. 0.724 in myelin water. Fittedε0was in good agreement with calculatedε0from directional diffusivities. Compared with those from healthy adult, the fitted, andαfrom neonates were substantially reduced butε0increased, consistent with incomplete myelination. Significant positiveand negative (αand) correlations were found with aging (demyelination) in elderly.ConclusionThe developed framework can better characterize orientation dependences from a wide range of proton transverse relaxation measurements in human brain WM, shedding new light on myelin microstructural alterations at the molecular level.
Hydrogen sulfide release via the ACE inhibitor Zofenopril prevents intimal hyperplasia in human vein segments and in a mouse model of carotid artery stenosis
Authors: Macabrey Diane , Deslarzes-Dubuis Céline , Longchamp Alban , Lambelet Martine , Ozaki Charles K. , Corpataux Jean-Marc , Allagnat Florent , Déglise Sébastien 
Published: September 2021

AbstractObjectivesHypertension is a major risk factor for intimal hyperplasia (IH) and restenosis following vascular and endovascular interventions. Pre-clinical studies suggest that hydrogen sulfide (H2S), an endogenous gasotransmitter, limits restenosis. While there is no clinically available pure H2S releasing compound, the sulfhydryl-containing angiotensin-converting enzyme inhibitor Zofenopril is a source of H2S. Here, we hypothesized that Zofenopril, due to H2S release, would be superior to other non-sulfhydryl containing angiotensin converting enzyme inhibitor (ACEi), in reducing intimal hyperplasia.MaterialsSpontaneously hypertensive male Cx40 deleted mice (Cx40−/−) or WT littermates were randomly treated with Enalapril 20 mg (Mepha Pharma) or Zofenopril 30 mg (Mylan SA). Discarded human vein segments and primary human smooth muscle cells (SMC) were treated with the active compound Enalaprilat or Zofenoprilat.MethodsIH was evaluated in mice 28 days after focal carotid artery stenosis surgery and in human vein segments cultured for 7 days ex vivo. Human primary smooth muscle cell (SMC) proliferation and migration were studied in vitro.ResultsCompared to control animals (intima/media thickness=2.3±0.33), Enalapril reduced IH in Cx40−/− hypertensive mice by 30% (1.7±0.35; p=0.037), while Zofenopril abrogated IH (0.4±0.16; p<.0015 vs. Ctrl and p>0.99 vs. sham-operated Cx40−/− mice). In WT normotensive mice, enalapril had no effect (0.9665±0.2 in control vs 1.140±0.27; p>.99), while Zofenopril also abrogated IH (0.1623±0.07, p<.008 vs. Ctrl and p>0.99 vs. sham-operated WT mice). Zofenoprilat, but not Enalaprilat, also prevented intimal hyperplasia in human veins segments ex vivo. The effect of Zofenopril on carotid and SMC correlated with reduced SMC proliferation and migration. Zofenoprilat inhibited the MAPK and mTOR pathways in SMC and human vein segments.ConclusionZofenopril provides extra beneficial effects compared to non-sulfhydryl ACEi to reduce SMC proliferation and restenosis, even in normotensive animals. These findings may hold broad clinical implications for patients suffering from vascular occlusive diseases and hypertension.Graphical AbstractWhat this paper addsThe current strategies to reduce intimal hyperplasia (IH) principally rely on local drug delivery, in endovascular approach. The oral angiotensin converting enzyme inhibitor (ACEi) Zofenopril has additional effects compared to other non-sulfyhydrated ACEi to prevent intimal hyperplasia and restenosis. Given the number of patients treated with ACEi worldwide, these findings call for further prospective clinical trials to test the benefits of sulfhydrated ACEi over classic ACEi for the prevention of restenosis in hypertensive patients.
Social modulation of oogenesis and egg-laying inDrosophila melanogaster
Authors: Bailly Tiphaine P. M. , Kohlmeier Philip , Etienne Rampal S. , Wertheim Bregje , Billeter Jean-Christophe 
Published: September 2021

AbstractBeing part of a group facilitates cooperation between group members, but also creates competition for limited resources. This conundrum is problematic for gravid females who benefit from being in a group, but whose future offspring may struggle for access to nutrition in larger groups. Females should thus modulate their reproductive output depending on their social context. Although social-context dependent modulation of reproduction is documented in a broad range of species, its underlying mechanisms and functions are poorly understood. In the fruit flyDrosophila melanogaster,females actively attract conspecifics to lay eggs on the same resources, generating groups in which individuals may cooperate or compete. The tractability of the genetics of this species allows dissecting the mechanisms underlying physiological adaptation to their social context.Here, we show that females produce eggs increasingly faster as group size increases. By laying eggs faster in group than alone, females appear to reduce competition between offspring and increase their likelihood of survival. In addition, females in a group lay their eggs during the light phase of the day, while isolated females lay them during the night. We show that responses to the presence of others are determined by vision through the motion detection pathway and that flies from any sex, mating status or species can trigger these responses. The mechanisms of this modulation of egg-laying by group is connected to a lifting of the inhibition of light on oogenesis and egg-laying by stimulating hormonal pathways involving juvenile hormone. Because modulation of reproduction by social context is a hallmark of animals with higher levels of sociality, our findings represent a protosocial mechanism in a species considered solitary that may have been the target of selection for the evolution of more complex social systems.
RTICBM-74 is a Brain-Penetrant CB1Receptor Allosteric Modulator that Reduces Alcohol Intake in Rats
Authors: Lovelock Dennis , Nguyen Thuy , Van Voorhies Kalynn , Zhang Yanan , Besheer Joyce 
Published: September 2021

ABSTRACTThe endocannabinoid system is implicated in the neuronal mechanisms of alcohol use disorder (AUD), with the cannabinoid receptor subtype 1 (CB1) representing a promising target for AUD therapeutic interventions. We have previously shown negative allosteric modulators (NAMs) of the CB1receptor attenuated the reinstatement of other drugs of abuse including cocaine and methamphetamine in rats; however, their effects on alcohol-related behaviors have not been investigated. Here, we tested the pharmacokinetic properties of one such CB1NAM, RTICBM-74, and its effects on alcohol self-administration in rats. RTICBM-74 showed low aqueous solubility and high protein binding but had excellent half-life and low clearance against rat liver microsomes and hepatocytes, and excellent brain penetrance in rats. RTICBM-74 pretreatment specifically reduced alcohol intake across a range of doses in male or female Wistar or Long-Evans rats that were trained to self-administer alcohol. These effects were similar to the CB1antagonist/inverse agonist rimonabant which was tested as a positive control. Importantly, RTICBM-74 was effective at reducing alcohol intake at doses that did not affect locomotion or sucrose self-administration. Our findings suggest that CB1NAMs such as RTICBM-74 have promising therapeutic potential in treatment of AUD.SIGNIFICANCE STATEMENTThe present work shows that a metabolically stable and brain penetrant CB1receptor negative allosteric modulator (NAM) reduces alcohol self-administration in rats without affecting locomotion or sucrose self-administration, suggesting potential therapeutic relevance for the treatment of AUD.
Single-Molecule Localization Microscopy of 3D Orientation and Anisotropic Wobble using a Polarized Vortex Point Spread Function
Authors: Ding Tianben , Lew Matthew D. 
Published: September 2021

AbstractWithin condensed matter, single fluorophores are sensitive probes of their chemical environments, but it is difficult to use their limited photon budget to image precisely their positions, 3D orientations, and rotational diffusion simultaneously. We demonstrate the polarized vortex point spread function (PSF) for measuring these parameters, including characterizing the anisotropy of a molecule’s wobble, simultaneously from a single image. Even when imaging dim emitters (∼500 photons detected), the polarized vortex PSF is able to obtain 12 nm localization precision, 4-8° orientation precision, and 26° wobble precision. We use the vortex PSF to measure the emission anisotropy of fluorescent beads, the wobble dynamics of Nile red (NR) within supported lipid bilayers, and the distinct orientation signatures of NR in contact with amyloid-beta fibrils, oligomers, and tangles. The unparalleled sensitivity of the vortex PSF transforms single-molecule microscopes into nanoscale orientation imaging spectrometers, where the orientations and wobbles of individual probes reveal structures and organization of soft matter that are nearly impossible to perceive using molecular positions alone.
A root for massive crown-of-thorns starfish outbreaks in the Pacific Ocean
Authors: Yasuda Nina , Inoue June , Hall Michael R. , Nair Manoj R. , Adjeroud Mehdi , Fortes Miguel D. , Nishida Mutsumi , Tuivavalagi Nat , Ravago-Gotanco Rachel , Forsman Zac H. , Hassan Soliman Taha Basheir , Koyanagi Ryo , Hisada Kanako , Motti Cherie A. , Satoh Noriyuki 
Published: September 2021

AbstractRecurring outbreaks of crown-of-thorns starfish (COTS) severely damage healthy corals in the Western Pacific Ocean. To determine the source of outbreaking COTS larvae and their dispersal routes across the Western Pacific, complete mitochondrial genomes were sequenced from 243 individuals collected in 11 reef regions. Our results indicate that Pacific COTS comprise two major clades, an East-Central Pacific clade (ECP-C) and a Pan-Pacific clade (PP-C). The ECP-C consists of COTS from French Polynesia (FP), Fiji, Vanuatu and the Great Barrier Reef (GBR), and does not appear prone to outbreaks. In contrast, the PP-C, which repeatedly spawns outbreaks, is a large clade comprising COTS from FP, Fiji, Vanuatu, GBR, Papua New Guinea, Vietnam, the Philippines, Japan, Micronesia, and the Marshall Islands. Given the nature of Pacific Ocean currents, the vast area encompassing FP, Fiji, Vanuatu, and the GBR likely supplies larvae for repeated outbreaks, exacerbated by anthropogenic environmental changes, such as eutrophication.
Life-history genotype explains variation in migration activity in Atlantic salmon (Salmo salar)
Authors: Niemelä Petri T. , Klemme Ines , Karvonen Anssi , Hyvärinen Pekka , Debes Paul V. , Erkinaro Jaakko , Sinclair-Waters Marion , Pritchard Victoria L. , Härkönen Laura , Primmer Craig R. 
Published: September 2021

AbstractOne of the most important life-history continuums is the fast–slow axis, where “fast” individuals mature earlier than “slow” individuals. “Fast” individuals are predicted to be more active than “slow” individuals; high activity is required to maintain a fast life-history strategy. Recent meta-analyses revealed mixed evidence for such integration. Here, we test whether known life-history genotypes differ in activity expression by using Atlantic salmon (Salmo salar) as a model. In salmon, variation in Vgll3, a transcription co-factor, explains ∼40% of variation in maturation timing. We predicted that the allele related to early maturation (vgll3*E) would be associated with increased activity. We used an automated surveillance system to follow ∼1900 juveniles including both migrants and non-migrants (i.e. smolt and parr fish, respectively) in semi-natural conditions over 31 days (∼580 000 activity measurements). Against our prediction,vgll3did not explain variation in activity in pooled migrant and non-migrant data. However, in migrants,vgll3explained variation in activity according to our prediction in a sex-dependent manner. Specifically, in females thevgll3*E allele was related to increasing activity, whereas in males thevgll3*L allele (later maturation allele) was related to increasing activity. These sex-dependent effects might be a mechanism maintaining within-population genetic life-history variation.
Weak selection and the separation of eco-evo time scales using perturbation analysis
Authors: Gerlee Philip 
Published: September 2021

AbstractWe show that under the assumption of weak frequency-dependent selection a wide class of population dynamical models can be analysed using perturbation theory. The inner solution corresponds to the ecological dynamics, where to zeroth order, the genotype frequencies remain constant. The outer solution provides the evolutionary dynamics and corresponds, to zeroth order, to a generalisation of the replicator equation. We apply this method to a model of public goods dynamics and construct, using matched asymptotic expansions, a composite solution valid for all times. We also analyse a Lotka-Volterra model of predator competition and show that to zeroth order the fraction of wild-type predators follows a replicator equation with a constant selection coefficient given by the predator death rate. For both models we investigate how the error between approximate solutions and the solution to the full model depend on the order of the approximation, and show using numerical comparison, for k = 1 and 2, that the error scales according to εk+1, where ε is the strength of selection and k is the order of the approximation.
The individuality of shape asymmetries of the human cerebral cortex
Authors: Chen Yu-Chi , Arnatkeviciute Aurina , McTavish Eugene , Pang James C. , Chopra Sidhant , Suo Chao , Fornito Alex , Aquino Kevin M. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: September 2021

AbstractAsymmetries of the cerebral cortex are found across diverse phyla and are particularly pronounced in humans, with important implications for brain function and disease. However, many prior studies have confounded asymmetries due to size with those due to shape. Here, we introduce a novel approach to characterize asymmetries of the whole cortical shape, independent of size, across different spatial frequencies using magnetic resonance imaging data in three independent datasets. We find that cortical shape asymmetry is highly individualized and robust, akin to a cortical fingerprint, and identifies individuals more accurately than size-based descriptors, such as cortical thickness and surface area, or measures of inter-regional functional coupling of brain activity. Individual identifiability is optimal at coarse spatial scales (∼37 mm wavelength), and shape asymmetries show scale-specific associations with sex and cognition, but not handedness. While unihemispheric cortical shape shows significant heritability at coarse scales (∼65 mm wavelength), shape asymmetries are determined primarily by subject-specific environmental effects. Thus, coarse-scale shape asymmetries are highly personalized, sexually dimorphic, linked to individual differences in cognition, and are primarily driven by stochastic environmental influences.
The role of superstition of cognitive control during neurofeedback training
Authors: Grössinger Doris , Fischmeister Florian Ph.S , Witte Matthias , Koschutnig Karl , Ninaus Manuel , Neuper Christa , Kober Silvia Erika , Wood Guilherme 
Published: September 2021

AbstractBackgroundReal-time fMRI neurofeedback is growing in reputation as a means to alter brain activity patterns and alleviate psychiatric symptoms. Activity in ventral striatum structures is considered an index of training efficacy. fMRI response in these brain regions indicates neurofeedback-driven associative learning. Here we investigated the impact of mere superstition of control as observed during neurofeedback training on patterns of fMRI activation.MethodsWe examined the brain activations of a large sample of young participants (n = 97, 50 female, age range 18-54yrs) in a simple fMRI task. Participants saw a display similar to that typically used for real-time fMRI. They were instructed to watch the bars’ movements or to control them with their own brain activity. Bar movements were not connected with brain activity of participants in any way and perceptions of control were superstitious. After the pretended control condition, they rated how well they were able to control the bars’ movements.ResultsStrong activation in the basal ganglia and ventral striatum as well as in large portions of the anterior insula, supplementary motor area, and the middle frontal gyrus due to the superstition of brain control.ConclusionsThe superstition of control over one’s own brain activity in a pretended neurofeedback training session activates the same neural networks as neurofeedback-driven learning. Therefore, activity in the basal ganglia and ventral striatum cannot be taken as evidence for neurofeedback-driven associative learning unless its effects are proven to supersede those elicited by appropriate sham conditions.
An improved culture protocol for the differentiation and survival of human promyelocytic leukaemia PLB-985 cell-line into mature neutrophil-like granulocytes
Authors: Shaayau Shehu , Cross Andrew L. , Wright Helen L. , Edwards Steven W. 
Published: September 2021

ABSTRACTCirculating blood neutrophils are short-lived, lack proliferation capacity and cannot be transfectedin vitroto express exogenous genes or proteins. These properties have made theex vivogenetic manipulation of neutrophils challenging and hindered biochemical and molecular studies investigating the function of specific genes and proteins. Improved methodology for differentiating cell lines into mature neutrophil-like phenotypes, with similar morphological and functional properties to blood neutrophils would, therefore, be an important tool to probe the molecular properties of mature cells. The PLB-985 cell line was cultured in RPMI-1640 medium supplemented foetal calf serum (FCS) and penicillin/streptomycin. For induction of differentiation into neutrophil-like cells, the medium was supplemented with sodium pyruvate,N, N-dimethylformamide (DMF) and all-transretinoic acid (ATRA), FCS and penicillin/streptomycin. The cytokines G-CSF and GM-CSF were used to enhance differentiation, prolong viability and delay the progression of the differentiated cells into apoptosis. The modified culture protocol and conditions induced PLB-985 cells to differentiate into mature, neutrophil-like granulocytes that resembled the morphology of mature blood neutrophils as evident by acquisition of a multi-lobed nucleus and granulated cytoplasm. These modified culture conditions resulted in enhanced differentiation into neutrophil-like cells and the apoptosis of these differentiated cells was delayed by supplementation with cytokines. This experimental system should be useful for studies probing the function of specific genes and proteins in human neutrophils.