bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulating overnight memory consolidation by acoustic stimulation during slow-wave sleep: a systematic review and meta-analysis
Authors: Wunderlin Marina , Züst Marc A , Hertenstein Elisabeth , Fehér Kristoffer D , Schneider Carlotta L , Klöppel Stefan , Nissen Christoph 
Published: January 2021

Abstract

Study Objectives
The low-frequency high-amplitude oscillations of slow-wave sleep (SWS) are considered to promote the consolidation of episodic memory. Previous research suggests that sleep slow waves can be entrained and enhanced by presenting short acoustic stimuli to the up-states of endogenous waves. Several studies have investigated the effects of these increases in slow-wave activity on overnight memory consolidation, with inconsistent results. The aim of this meta-analysis was to evaluate the accumulated evidence connecting acoustic stimulation during sleep to episodic memory consolidation.

Methods
A systematic literature search was conducted in October 2020 using PubMed, Web of Science, and PsycInfo. The main study inclusion criteria were the application of acoustic slow wave enhancement in healthy participants and an assessment of pre- and post-sleep episodic memory performance. Effect sizes were pooled using a random-effects model.

Results
A total of 10 primary studies with 11 experiments and 177 participants were included. Results showed a combined effect size (Hedges’ g) of 0.25 (p = 0.07). Subgroup models based on young adults (n = 8), phase-locked stimulation approaches (n = 8), and their combination (n = 6) showed combined effect sizes of 0.31 (p = 0.051), 0.36 (p = 0.047), and 0.44 (p = 0.01), respectively. There was no indication of publication bias or bias in individual studies.

Conclusions
Acoustic enhancement of SWS tends to increase the overnight consolidation of episodic memory but effects remain small and—with the exception of subgroup models—at trend levels. Currently, the evidence is not sufficient to recommend the use of commercially available devices.
Memory-relevant nap sleep physiology in healthy and pathological aging
Authors: Ladenbauer Julia , Ladenbauer Josef , Külzow Nadine , Flöel Agnes 
Published: January 2021

AbstractStudy ObjectivesAging is associated with detrimental changes in sleep physiology, a process accelerated in Alzheimer’s disease. Fine-tuned temporal interactions of non-rapid eye movement slow oscillations and spindles were shown to be particularly important for memory consolidation, and to deteriorate in healthy older adults. Whether this oscillatory interaction further decline in early stages of Alzheimer’s disease such as mild cognitive impairment has not been investigated to date, but may have important therapeutic implications.MethodsHere, we assessed differences in sleep architecture and memory-relevant slow oscillation, sleep spindles and their functional coupling during a 90-min nap between healthy young and older adults, and in older patients with mild cognitive impairment. Furthermore, associations of nap-sleep characteristics with sleep-dependent memory performance change were evaluated.ResultsWe found significant differences between young and older healthy adults, and between young adults and patients with mild cognitive impairment, but not between healthy older adults and patients for several sleep metrics, including slow oscillation-spindle coupling. Moreover, sleep-dependent retention of verbal memories was significantly higher in young healthy adults versus older adults with and without mild cognitive impairment, but no difference between the two older groups was observed. Associations with sleep metrics were only found for pre-nap memory performances.ConclusionsIn conclusion, our results indicate changes in nap sleep physiology and sleep-related memory consolidation in older adults with and without mild cognitive impairment. Thus, interventions targeted at improving sleep physiology may help to reduce memory decline in both groups, but our study does not indicate additional benefits for patients with mild cognitive impairment.Clinical Trail RegistrationEffects of Brain Stimulation During Daytime Nap on Memory Consolidation in Younger, Healthy Subjects: https://clinicaltrials.gov/ct2/show/NCT01840865; NCT01840865. Effects of Brain Stimulation During a Daytime Nap on Memory Consolidation in Older Adults; https://clinicaltrials.gov/ct2/show/study/NCT01840839?term=01840839&draw=2&rank=1; NCT01840839. Effects of Brain Stimulation During a Daytime Nap on Memory Consolidation in Patients With Mild Cognitive Impairment; https://clinicaltrials.gov/ct2/show/NCT01782365?term=01782365&draw=2&rank=1; NCT01782365.
Molecular mechanism of mice gastric oxidative damage induced by nanoparticulate titanium dioxide
Authors: Ji Jianhui , Zhou Yingjun , Hong Fashui , Ze Yuguan , Fan Dongxue , Zhang Xingxiang 
Published: January 2021

Abstract

Background
Nanoparticulate titanium dioxide (Nano-TiO2) has been widely used in food industry, and it has been demonstrated to have adverse effects on mice and human stomach, but its mechanism is rarely concerned. The aim of this study is to determine the effects of nano-TiO2 on the stomach and confirm the role of oxidative stress and apoptosis in the mice gastric damage caused by nano-TiO2, as well as its molecular mechanisms.

Methods
Mice were continuously exposed to nano-TiO2 with 1.25, 2.5 and 5 mg/kg bw by intragastric administration for 9 months in the present study. The ultrastructure, levels of reactive oxygen species (ROS) and peroxides, activities of antioxidant enzymes and mitochondria-related enzymes, ATP contents as well as apoptosis-related factors expression in mice stomach were examined.

Results
Oxidative stress, apoptosis and nano-TiO2 aggregation were found in gastric mucosal smooth muscle cells after nano-TiO2 exposure. Nano-TiO2 exposure also resulted in the over-production of ROS and peroxides, decrease of ATP production and activities of antioxidant enzymes and mitochondria-related ATPases, upregulation of apoptosis-related factors including γH2AX, Cyt c, caspase 3, and p-JNK expression, and down-regulation of Bcl-2 expression in mice stomach.

Conclusions
The gastric toxicity of mice induced by chronic exposure to low dose nano-TiO2 may be associated with oxidative stress and mitochondria-mediated apoptosis in mice.
Protective effect of melatonin against herbicides-induced hepatotoxicity in rats
Authors: Almeida Lécio Leone , Pitombeira Giovanna Silva Girão Nobre , Teixeira Álvaro Aguiar Coelho , Teixeira Valéria Wanderley , Silva Júnior Valdemiro Amaro , Vieira Filho Leucio Duarte , Evêncio Neto Joaquim 
Published: January 2021

Abstract
Exposure to the herbicides Paraquat and Roundup® may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the liver. The aim of this study was to analyze the effect of melatonin on liver of rats exposed to herbicides. A total of 35 rats were randomly divided into seven equal-sized groups: control, Paraquat, Roundup®, Paraquat + Roundup®, Paraquat + melatonin, Roundup® + melatonin, and Paraquat + Roundup® + melatonin. Samples of blood and hepatic tissue were collected at the end of the seventh day of exposure and treatment with melatonin. Body weight, hematological parameters, and histopathological, biochemical analyses and determination of oxidative stress levels in liver were evaluated. Body weight was compromised (P &lt; 0.01). Alterations of hematologic parameters were significant when compared to control (P &lt; 0.001). Biochemically, serum levels of albumin decreased (P &lt; 0.001), but serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased (P &lt; 0.001). Histopathology revealed necrotic hepatocytes, portal and central-lobular inflammatory infiltrate, congestion of capillaries. Serum levels of thiobarbituric acid reactive substances were found to be significantly elevated (P &lt; 0.05; P &lt; 0.001), and serum level of reduced glutathione was significantly lower (P &lt; 0.05; P &lt; 0.001). The groups treated concomitantly with melatonin revealed results similar to those of the control. However, melatonin acted as a protective agent for the liver against experimentally induced hepatic toxicity, promoting prevention of body weight, oxidative stress, and normalization of hematological and biochemical parameters.
Comet assay: a versatile but complex tool in genotoxicity testing
Authors: Cordelli Eugenia , Bignami Margherita , Pacchierotti Francesca 
Published: January 2021

Abstract
The comet assay is a versatile method for measuring DNA strand breaks in individual cells. It can also be applied to cells isolated from treated animals. In this review, we highlight advantages and limitations of this in vivo comet assay in a regulatory context. Modified versions of the standard protocol detect oxidized DNA bases and may be used to reveal sites of DNA base loss, DNA interstrand crosslinks, and the extent of DNA damage induced indirectly by reactive oxygen species elicited by chemical-induced oxidative stress. The assay is, however, at best semi-quantitative, and we discuss possible approaches to improving DNA damage quantitation and highlight the necessity of optimizing protocol standardization to enhance the comparability of results between laboratories. As a genotoxicity test in vivo, the in vivo comet assay has the advantage over the better established micronucleus erythrocyte test that it can be applied to any organ, including those that are specific targets of chemical carcinogens or those that are the first sites of contact of ingested or inhaled mutagens. We illustrate this by examples of its use in risk assessment for the food contaminants ochratoxin and furan. We suggest that improved quantitation is required to reveal the full potential of the comet assay and enhance its role in the battery of in vivo approaches to characterize the mechanisms of toxicity and carcinogenicity of chemicals and to aid the determination of safe human exposure limits.
Ivermectin as a potential treatment for mild to moderate COVID-19 – A double blind randomized placebo-controlled trial
Authors: Ravikirti  , Roy Ranjini , Pattadar Chandrima , Raj Rishav , Agarwal Neeraj , Biswas Bijit , Majhi Pramod Kumar , Rai Deependra Kumar , Shyama  , Kumar Anjani , Sarfaraz Asim 
Published: January 2021

AbstractObjectiveIvermectin has been suggested as a treatment for COVID-19.This randomised control trial was conducted to test the efficacy of Ivermectin in the treatment of mild and moderate COVID-19.DesignParallel, double blind, randomised, placebo controlled trial Setting: A tertiary care dedicated COVID-19 hospital in Bihar, IndiaParticipantsAdult patients (> 18 years) admitted with mild to moderate COVID 19 disease (saturation > 90% on room air, respiratory rate < 30 and no features of shock) with no contraindications to ivermectin and willing to participate in the studyInterventionPatients in the intervention arm were given ivermectin 12 mg on day 1 and day 2 of admission. Patients in the placebo arm were given identical looking placebo tablets. Rest of the treatment was continued as per the existing protocol and the clinical judgment of the treating teams.Outcome MeasuresThe primary outcome measure was a negative RT-PCR test for SARS-CoV-2 on day 6 of admission. The secondary outcome measures were symptom status on day 6, discharge status on day 10, admission to ICU, need for invasive mechanical ventilation and in-hospital mortality.ResultsA total of 115 patients were enrolled for the study of which 112 were included in the final analysis. Of them, 55 were randomised to the intervention arm while 57 were randomised to the placebo arm. There was no significant difference in the baseline characteristics of the two arms. There was no significant difference in the primary outcome, i.e. negative RT-PCR status on day 6 between the two groups. Similarly, there was no significant difference between the two groups in most of the secondary outcome measures, viz. symptom status on day 6, discharge status on day 10, admission to ICU, and need for invasive mechanical ventilation. However, while there was no in-hospital mortality in the intervention arm, there were 4 deaths in the placebo arm. As a result, all patients in the intervention arm (n=56) were successfully discharged as compared to 93.1% (n=54/58) in the placebo arm (RR 1.1, 95% CI 1.0 to 1.2, p=0.019).ConclusionThere was no difference in the primary outcome i.e. negative RT-PCR status on day 6 of admission with the use of ivermectin. However, a significantly higher proportion of patients were discharged alive from the hospital when they received ivermectin.Strengths and Limitations of the StudyThis study was randomised and double blind, thereby minimizing the chance of bias.All outcome measures except symptom status on day 6 were objective and placebo control was used for comparison.Only single repeat RT-PCR was done. So median time to viral clearance in the two groups could not be calculated.Severe cases were not included in the study.
Microglia deficiency accelerates prion disease but does not enhance prion accumulation in the brain
Authors: Bradford Barry M. , McGuire Lynne I. , Hume David A. , Pridans Clare , Mabbott Neil A. 
Published: January 2021

AbstractPrion diseases are transmissible, neurodegenerative disorders associated with misfolding of the prion protein. Previous studies show that reduction of microglia accelerates CNS prion disease and increases the accumulation of prions in the brain, suggesting that microglia provide neuroprotection by phagocytosing and destroying prions. InCsf1rΔFIREmice, the deletion of an enhancer withinCsf1rspecifically blocks microglia development, however, their brains develop normally and show none of the deficits reported in other microglia-deficient models.Csf1rΔFIREmice were used as a refined model in which to study the impact of microglia-deficiency on CNS prion disease. AlthoughCsf1rΔFIREmice succumbed to CNS prion disease much earlier than wild-type mice, the accumulation of prions in their brains was reduced. Instead, astrocytes displayed earlier, non-polarized reactive activation with enhanced synaptic pruning and unfolded protein responses. Our data suggest that rather than simply phagocytosing and destroying prions, the microglia instead provide host-protection during CNS prion disease and restrict the harmful activities of reactive astrocytes.Main pointsCNS prion disease is accelerated in mice completely lacking microglia. The rate of prion accumulation in the brain was unaltered in absence of microglia. Microglia provide host-protection during CNS prion disease independent of prion clearance.
Chromosome fusion affects genetic diversity and evolutionary turnover of functional loci, but consistently depends on chromosome size
Authors: Cicconardi Francesco , Lewis James J , Martin Simon H , Reed Robert D. , Danko Charles G , Montgomery Stephen H 
Published: January 2021

AbstractMajor changes in chromosome number and structure are linked to a series of evolutionary phenomena, including intrinsic barriers to gene flow or suppression of recombination due to chromosomal rearrangements. However, chromosome rearrangements can also affect the fundamental dynamics of molecular evolution within populations by changing relationships between linked loci and altering rates of recombination. Here, we build chromosome-level assemblyEueides isabellaand, together with the chromosome-level assembly ofDryas iulia, examine the evolutionary consequences of multiple chromosome fusions inHeliconiusbutterflies. These assemblies pinpoint fusion points on 10 of the 21 autosomal chromosomes and reveal striking differences in the characteristics of fused and unfused chromosomes. The ten smallest autosomes inD. iuliaandE. isabella, which have each fused to a longer chromosome inHeliconius, have higher repeat and GC content, and longer introns than predicted by their chromosome length. Following fusion, these characteristics change to become more in line with chromosome length. The fusions also led to reduced diversity, which likely reflects increased background selection and selection against introgression between diverging populations, following a reduction in per-base recombination rate. We further show that chromosome size and fusion impact turnover rates of functional loci at a macroevolutionary scale. Together these results provide further evidence that chromosome fusion inHeliconiuslikely had dramatic effects on population level processes shaping rates of neutral and adaptive divergence. These effects may have impacted patterns of diversification inHeliconius, a classic example of an adaptive radiation.
Periodicity in the embryo: emergence of order in space, diffusion of order in time
Authors: Alicea Bradly , Parent Jesse , Singh Ujjwal 
Published: January 2021

AbstractDoes embryonic development exhibit characteristic temporal features? This is apparent in evolution, where evolutionary change has been shown to occur in bursts of activity. Using two animal models (Nematode,Caenorhabditis elegansand Zebrafish,Danio rerio) and simulated data, we demonstrate that temporal heterogeneity exists in embryogenesis at the cellular level, and may have functional consequences. Cell proliferation and division from cell tracking data is subject to analysis to characterize specific features in each model species. Simulated data is then used to understand what role this variation might play in producing phenotypic variation in the adult phenotype. This goes beyond a molecular characterization of developmental regulation to provide a quantitative result at the phenotypic scale of complexity.
Myeloperoxidase-induced fibrinogen unfolding and clotting
Authors: Barinov Nikolay A. , Pavlova Elizaveta R. , Tolstova Anna P. , Dubrovin Evgeniy V. , Klinov Dmitry V. 
Published: January 2021

AbstractFibrinogen is a major protein of blood coagulation system and is a promising component of biomaterials and protein matrixes. Conformational changes of fibrinogen underlie the important mechanism of thrombin mediated fibrinogen clotting but also may induce the loss of its biological activity and (amyloid) aggregation. Understanding and controlling of fibrinogen unfolding is important for the development of fibrinogen based materials with tunable properties. We have discovered that myeloperoxidase induces denaturation of fibrinogen molecules followed by fibrinogen clotting, which is not thrombin-dependent. This is the first example of ATP-independent, non-targeted protein-induced protein denaturation. The morphological structure of unfolded fibrinogen molecules and “non-conventional” fibrinogen clots has been characterized using high-resolution atomic force microscopy and scanning electron microscopy techniques. Circular dichroism (CD) spectroscopy has shown no significant changes of the secondary structure of the fibrinogen clots. The absorbance spectrophotometry has demonstrated that the kinetics of myeloperoxidase induced fibrinogen clotting strongly decays with growth of ionic strength indicating a major role of the Debye screening effect in regulating of this process. The obtained results provide with the novel concepts of protein unfolding and open new insights into fibrinogen clotting. Moreover, they give new possibilities in biotechnological and biomedical applications, e.g., for regulation of fibrinogen clotting and platelet adhesion and for the development of fibrinogen-based matrices.The organization of a protein molecule is characterized by different hierarchical levels such as primary, secondary, tertiary and quaternary structure. Protein unfolding or denaturation, i.e. its transformation to a lower order structure (and loss of a higher order structure), is a biologically and biotechnologically relevant process. Protein unfolding is a prerequisite for an alternative folding pathway including amyloid aggregation1,2. Unfolded proteins may be used in development of protein films and coatings with special properties such as enhanced mechanical stability3–5, resistance to protein adsorption or platelet adhesion6,7and other advantages8. Unfolding of a protein molecule may lead to the loss of its biological function9that has important consequences in biosensor10,11and pharmaceutical applications12.
Dysregulation of the basal ganglia indirect pathway prior to cell loss in the Q175 mouse model of Huntington’s disease
Authors: Callahan Joshua W. , Wokosin David L. , Bevan Mark D. 
Published: January 2021

AbstractThe psychomotor symptoms of Huntington’s disease (HD) are linked to degeneration of the basal ganglia indirect pathway. To determine how this pathway is perturbed prior to cell loss, optogenetic- and reporter-guided electrophysiological interrogation approaches were applied to early symptomatic 6-month-old Q175 HD mice. Although cortical activity was unaffected, indirect pathway striatal projection neurons were hypoactivein vivo, consistent with reduced cortical input strength and dendritic excitability. Downstream parvalbumin-expressing prototypic external globus pallidus (GPe) neurons were hyperactivein vivoand exhibited elevated autonomous firingex vivo. Optogenetic inhibition of prototypic GPe neurons ameliorated the abnormal hypoactivity of postsynaptic subthalamic nucleus (STN) and putative arkypallidal neuronsin vivo. In contrast to STN neurons, autonomous arkypallidal activity was unimpairedex vivo. Together with previous studies, these findings demonstrate that basal ganglia indirect pathway neurons are highly dysregulated in Q175 mice through changes in presynaptic activity and/or intrinsic properties 6-12 months before cell loss.
Disrupted PDZ-domain binding motif of the dopamine transporter uniquely alters nanoscale distribution, dopamine homeostasis and reward motivation
Authors: Sørensen Gunnar , Rickhag Mattias , Leo Damiana , Lycas Matthew D. , Ridderstrøm Pernille Herrstedt , Weikop Pia , Herborg Freja , Woldbye David , Wörtwein Gitta , Gainetdinov Raul R. , Fink-Jensen Anders , Gether Ulrik 
Published: January 2021

AbstractThe dopamine transporter (DAT) is part of a presynaptic multi-protein network involving interactions with scaffold proteins via its C-terminal PDZ-domain binding sequence. In a mouse model expressing DAT with mutated PDZ binding sequence (DAT-AAA), we previously demonstrated the importance of this binding sequence for striatal expression of DAT. Here we show by application of direct Stochastic Reconstruction Microscopy (dSTORM) not only that the striatal level of transporter is reduced in DAT-AAA mice, but also that the nanoscale distribution of the transporter is altered with a higher propensity of DAT-AAA to localize to irregular nanodomains in dopaminergic terminals. In parallel, we observe mesostriatal dopamine (DA) adaptations and changes in DA-related behaviors different from those seen in other genetic DAT mouse models. DA levels in striatum are reduced to ∼45% of wild type (WT), accompanied by elevated DA turnover. Nonetheless, Fast-Scan Cyclic Voltammetry recordings on striatal slices reveal a larger amplitude and prolonged clearance rate of evoked DA release in DAT-AAA mice compared to WT mice. Autoradiography and radioligand binding show reduced DA D2 receptor levels while immunohistochemistry and autoradiography show unchanged DA D1 receptor levels. In behavioral experiments, we observe enhanced self-administration of liquid food under both a fixed-ratio (FR1) and progressive-ratio (PR) schedule of reinforcement, but a reduction compared to WT when using cocaine as reinforcer. Summarized, our data demonstrate how disruption of PDZ-domain interactions causes changes in DAT expression and its nanoscopic distribution that in turn alter DA clearance dynamics.