bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitotic chromatin marking governs asymmetric segregation of DNA damage
Authors: Ferrand Juliette , Dabin Juliette , Chevallier Odile , Kane-Charvin Matteo , Kupai Ariana , Hrit Joel , Rothbart Scott B. , Polo Sophie E. 
Published: September 2023

SUMMARYThe faithful segregation of intact genetic material and the perpetuation of chromatin states through mitotic cell divisions are pivotal for maintaining cell function and identity across cell generations. However, most exogenous mutagens generate long-lasting DNA lesions that are segregated during mitosis. How this segregation is controlled is unknown. Here, we uncover a mitotic chromatin-marking pathway that governs the segregation of UV-induced damage in human cells. Our mechanistic analyses reveal two layers of control: histone ADP-ribosylation, and the incorporation of newly synthesized histones at UV damage sites, that both prevent local mitotic phosphorylations on histone H3 serine residues. Functionally, this chromatin-marking pathway drives the asymmetric segregation of UV damage in the cell progeny with consequences on daughter cell fate. We propose that this mechanism may help preserve the integrity of stem cell compartments during asymmetric cell divisions.
Male-biased stone tool use by wild white-faced capuchins (Cebus capucinus imitator)
Authors: Goldsborough Zoë , Crofoot Margaret C. , Barrett Brendan J. 
Published: September 2023

AbstractTool-using primates often show sex differences in both the frequency and efficiency of tool use. In species with sex-biased dispersal, such within-group variation likely shapes patterns of cultural transmission of tool-use traditions between groups. On the Panamanian islands of Jicarón and Coiba, a population of white-faced capuchins (Cebus capucinus imitator)—some of which engage in habitual stone tool use—provide an opportunity to test hypotheses about why such sex-biases arise. On Jicarón, we have only observed males engaging in stone tool use, whereas on Coiba, both sexes are known to use tools. Using 5 years of camera trap data, we show that this variation reflects a true sex difference in tool use rather than a sampling artefact, and then test hypotheses about the factors driving this pattern. Differences in physical ability or risk-aversion, and competition over access to anvils do not account for the sex-differences in tool-use we observe. Our data show that females are physically capable of stone tool use: females on Coiba and juveniles on Jicarón as small and smaller than adult females regularly engage in tool use. Females also have ample opportunity to use tools: the sexes are equally terrestrial, and competition over anvils is low. Finally, females rarely scrounge on left-over food items either during or after tool-using events, suggesting they are not being provisioned by males. Although it remains unclear why white-faced capuchin females on Jicarón do not use stone-tools, our results illustrate that such sex biases in socially learned behaviors can arise even in the absence of obvious physical, environmental and social constraints. This suggests that a much more nuanced understanding of the differences in social structure, diet and dispersal patterns are needed to explain why sex-biases in tool use arise in some populations but not in others.
Transcranial Focused Ultrasound to V5 Enhances Human Visual Motion Brain-Computer Interface by Modulating Feature-Based Attention
Authors: Kosnoff Joshua , Yu Kai , Liu Chang , He Bin 
Published: September 2023

AbstractParalysis affects roughly 1 in 50 Americans. While there is no cure for the condition, brain-computer interfaces (BCI) can allow users to control a device with their mind, bypassing the paralyzed region. Non-invasive BCIs still have high error rates, which is hypothesized to be reduced with concurrent targeted neuromodulation. This study examines whether transcranial focused ultrasound (tFUS) modulation can improve BCI outcomes, and what the underlying mechanism of action might be through high-density electroencephalography (EEG)-based source imaging (ESI) analyses. V5-targeted tFUS significantly reduced the error for the BCI speller task. ESI analyses showed significantly increased theta activity in the tFUS condition at both V5 and downstream the dorsal visual processing pathway. Correlation analysis indicates that the dorsal processing pathway connection was preserved during tFUS stimulation, whereas extraneous connections were severed. These results suggest that V5-targeted tFUS’ mechanism of action is to raise the brain’s feature-based attention to visual motion.
Spontaneous dynamics of hippocampal place fields in a model of combinatorial competition among stable inputs
Authors: Savelli Francesco 
Published: September 2023

AbstractWe present computer simulations illustrating how the plastic integration of spatially stable inputs could contribute to the dynamic character of hippocampal spatial representations. In novel environments of slightly larger size than typical apparatus, the emergence of well-defined place fields in real place cells seems to rely on inputs from normally functioning grid cells. Theoretically, the grid-to-place transformation is possible if a place cell is able to respond selectively to a combination of suitably aligned grids. We previously identified the functional characteristics that allow a synaptic plasticity rule to accomplish this selection by synaptic competition during rat foraging behavior. Here, we show that the synaptic competition can outlast the formation of place fields, contributing to their spatial reorganization over time, when the model is run in larger environments and the topographical/modular organization of grid inputs is taken into account. Co-simulated cells that differ only by their randomly assigned grid inputs display different degrees and kinds of spatial reorganization—ranging from place-field remapping to more subtle in-field changes or lapses in firing. The model predicts a greater number of place fields and propensity for remapping in place cells recorded from more septal regions of the hippocampus and/or in larger environments, motivating future experimental standardization across studies and animal models. In sum, spontaneous remapping could arise from rapid synaptic learning involving inputs that are functionally homogeneous, spatially stable, and minimally stochastic.Significance StatementIn both AI and theoretical neuroscience, learning systems often rely on the asymptotic convergence of slow-acting learning rules applied to input spaces that are presumed to be sampled repeatedly, for example over developmental timescales. Place cells of the hippocampus testify to a neural system capable of rapidly encoding cognitive variables—such as the animal’s position in space—from limited experience. These internal representations undergo “spontaneous” changes over time, spurring much interest in their cognitive significance and underlying mechanisms. We investigate a model suggesting that some of these changes could be a tradeoff of rapid learning.
3D human retinal organoid model for the study of early diabetic retinopathy
Authors: de Lemos Luisa , Antas Pedro , Ferreira Inês S. , Santos Inês Paz , Gomes Catarina M. , Brito Catarina , Seabra Miguel C. , Tenreiro Sandra 
Published: September 2023

AbstractDiabetic retinopathy (DR) is a significant complication of diabetes and a primary cause of visual impairment among working-age individuals. DR is a degenerative condition in which hyperglycaemia results in morphological and functional changes in certain retinal cells. Existing treatments mainly address the advanced stages of the disease, which involve vascular defects such as macular edema or neovascularization. However, it is now known that retinal neurodegeneration and inflammation precede these vascular changes. Therefore, there is a pressing need to identify new therapeutic approaches that target the early stages of DR and prevent its progression.In the last decade, the development of reliablein vitromodels resembling the complexity of the retinal tissue has significantly improved. Namely, three-dimensional (3D) retinal organoids derived from human induced-pluripotent stem cells (hiPSCs) recapitulate the cellular organization and complexity of the human retina.Here, we used hiPSCs-derived retinal organoids to generate a model of early DR. In this model, we observe well-established molecular and cellular features of early DR:i) loss of retinal ganglion and amacrine cells;ii) glial reactivity and inflammation, with increased expression of the vascular endothelial-derived growth factor (VEGF)and interleukin-1β (IL-1β),and monocyte chemoattractant protein-1 (MCP-1) secretion;iii) increased levels of reactive oxygen species accompanied by activation of key enzymes involved in antioxidative stress response. The data provided highlight the utility of retinal organoid technology in modelling early-stage DR. This offers new avenues for the development of targeted therapeutic interventions on neurodegeneration and inflammation in the initial phase of DR, potentially slowing the disease’s progression.
Psychometric properties of the Perceived Stress Scale-4 (PSS-4) in Colombians with university education
Authors: Sanabria-Mazo Juan P. , Gómez-Acosta Andrés , Annicchiarico-Lobo Julio , Luciano Juan V. , Sanz Antoni 
Published: September 2023

AbstractThe Perceived Stress Scale-4 (PSS-4) is an ultra-brief self-report measure to assess perceived psychological stress. This study evaluated the psychometric properties of the PSS-4 in Colombia. A total of 1911 adult participants with university education completed the PSS-4. Characteristics of the items and the subscales were explored. Dimensionality was assessed using confirmatory factor analysis (CFA), incorporating an examination of invariance (configural, metric, scalar, and strict) across socio-demographic characteristics. Construct validity (convergent and discriminant), reliability indices, know-groups, and predictive validity were also computed. The CFA showed adequate fit indices for the two-factor model (hopelessness and coping), being invariant across gender, income level, age, and work status. Internal consistency was adequate for the PSS-4 (α= .73,ω= .72,λ2= .74). Significant positive correlations of the PSS-4 were identified with depression (r= .59) and anxiety (r= .55), as well as significant negative with post-traumatic growth (r= –.37) and resilience (r= –.47). The PSS-4 showed adequate capacity to predict potential depressive and anxiety symptoms, as well as protective factors such as resilience and posttraumatic growth. Higher scores on the PSS-4 were observed among young people, as well as among people with lower incomes and those unemployed. These findings suggest that the PSS-4 can be a reliable and valid tool for assessing psychological stress in Colombians with university education.
Targeted and optimized multi-channel transcranial direct current stimulation for focal epilepsy: An N-of-1 trial
Authors: Antonakakis Marios , Kaiser Fabian , Rampp Stefan , Kovac Stjepana , Wiendl Heinz , Stummer Walter , Gross Joachim , Kellinghaus Christoph , Khaleghi-Ghadiri Maryam , Möddel Gabriel , Wolters Carsten H. 
Published: September 2023

AbstractTranscranial direct current stimulation (tDCS) has been used to noninvasively reduce epileptic activity in focal epilepsy. In this proof-of-principle N-of-1 trial in a patient with drug-resistant focal epilepsy, we propose distributed constrained maximum intensity (D-CMI) for individually targeted and optimized multi-channel (mc-) tDCS to reduce epileptic activity. Combined electro- and magnetoencephalography (EMEG) source analysis in a realistic calibrated head model defines location and orientation of the target epileptogenic source. Converging evidence for this determination is achieved by retrospective identification of a cortical malformation in magnetic resonance imaging and by successful EMEG-guided invasive EEG. We applied D-CMI in a double-blind, sham-controlled stimulation experiment. In two stimulation weeks, either D-CMI or sham stimulation with 4 mA injection current were applied twice every week-day for 20 min each, with a 20 min pause in between. EEG was recorded 1 h before and after stimulation. For D-CMI, we find a highly significant reduction in IED frequency (p < 0.0001) marked by three experts of on average 37% to 81% over the five days of stimulation (mean ± SD: 58% ± 19%), while this is not the case for sham. The proposed procedure was well-tolerated and parameterizes a group clinical trial (Study registration number: DRKS00029384).
Segment-specific axon guidance by Wnt/Fz signaling diversifies motor commands inDrosophilalarvae
Authors: Takagi Suguru , Takano Shiina , Hashimoto Yusaku , Morise Shu , Zeng Xiangsunze , Nose Akinao 
Published: September 2023

AbstractFunctional diversification of homologous neuronal microcircuits is a widespread feature observed across brain regions as well as across species, while its molecular and developmental mechanisms remain largely unknown. We address this question inDrosophilalarvae by focusing on segmentally homologous Wave command-like neurons, which diversify their wiring and function in a segment-specific manner. Anterior Wave (a-Wave) neurons extend axons anteriorly and connect to circuits inducing backward locomotion, whereas posterior Wave (p-Wave) neurons extend axons posteriorly and trigger forward locomotion. Here, we show that Frizzled receptors DFz2 and DFz4, together with the DWnt4 ligand, regulate the segment-specific Wave axon projection.DFz2knock-down (KD) not only reroutes Wave axons to posterior neuromeres but also biases its motor command to induce forward instead of backward locomotion as tactile response. Thus, segment-specific axon guidance diversifies the function of homologous command neurons in behavioral regulation. Since control of anterior-posterior (A-P) axon guidance by Wnt/Fz-signaling is evolutionarily conserved, our results reveal a potentially universal molecular principle for formation and diversification of the command system in the nerve cord. Furthermore, this work indicates that sensorimotor transduction can be rerouted by manipulating a single gene in a single class of neurons, potentially facilitating the evolutionary flexibility in action selection.Impact statementRewiring the command neurons in the tactile circuit suffices to change the behavioral strategy of a whole animal, implying a “plug-and-play” flexibility in sensorimotor circuits.
Rethinking sinking: Imaging flow fields of natural marine aggregates to infer porosity-dependent changes in sinking velocity and carbon flux
Authors: Flintrop Clara M. , Ahmerkamp Soeren , Moradi Nasrollah , Klawonn Isabell , März Jöran , Hörstmann Cora , Kiko Rainer , Khalili Arzhang , Grossart Hans-Peter , Álvarez-Salgado Xosé A. , Arístegui Javier , Iversen Morten H. 
Published: September 2023

AbstractThe marine biological carbon pump is mainly driven by the interplay between aggregate sinking velocity and remineralization. Sinking velocity of natural marine aggregates is not routinely measured but often calculated using Stokes’ law, which does not consider size-dependent changes in porosity. We analyzed the flow fields around 81in situ-formed aggregates using Particle Image Velocimetry (PIV) to determine the factors controlling aggregate settling. Using an independently derived scaling of porosity with size, we predicted the sinking velocity of laboratory-formed andin situ-formed aggregates with known densities. Small aggregates (<500 µm) have relatively lower porosities than large aggregates, and their increased compactness and density leads to higher size-specific settling velocities, and generally higher carbon-to-volume ratios. Applying our scaling approach to a global data set of vertical aggregate abundance and size distribution, we found that small aggregates contribute 40-70% to total carbon fluxesin situ.TeaserImproved sinking velocity prediction for marine aggregates highlights the contribution of small aggregates to carbon sequestration.
Naturally occurring viruses ofDrosophilareduce offspring number and lifespan
Authors: Wallace Megan A. , Obbard Darren J. 
Published: September 2023

AbstractDrosophilaremains a pre-eminent insect model system for host-virus interaction, but the host range and fitness consequences of the drosophilid virome are poorly understood. Metagenomic studies have reported over 160 viruses associated withDrosophilidae, but few isolates are available to characterise theDrosophilaimmune response, and most characterisation has relied on injection and systemic infection. Here we use a more natural infection route to characterise the fitness effects of infection and to study a wider range of viruses. We exposed laboratoryD. melanogasterto 23 naturally occurring viruses from wild-collected drosophilids. We recorded transmission rates along with two components of female fitness: survival and the lifetime number of adult offspring produced. Nine different viruses transmitted during contact with laboratoryD. melanogaster, although for the majority, rates of transmission were less than 20%. Five virus infections led to a significant decrease in lifespan (D. melanogaster nora virus, D. immigrans nora virus, Muthill virus, galbut virus and Prestney Burn virus), and three led to a reduction in the total number of offspring. Our findings demonstrate the utility of theDrosophilamodel for community-level studies of host-virus interactions, and suggest that viral infection could be a substantial fitness burden on wild flies.
Identification of an osteopontin-derived peptide that binds neuropilin-1 and activates vascular cells
Authors: Chen Yihong , Gialeli Chrysostomi , Shen Junyan , Dunér Pontus , Walse Björn , Duelli Annette , Caing-Carlsson Rhawnie , Blom Anna M. , Zibert John , Hultgårdh Nilsson Anna , Alenfall Jan , Liang Chun , Nilsson Jan 
Published: September 2023

AbstractBackgroundThe osteopontin-derived peptide FOL-005 has been shown to stimulate hair growth. Using ligand-receptor glycocapture technology we identified neuropilin-1 (NRP-1), a known co-receptor for vascular endothelial growth factor (VEGF) receptors, as the most probable receptor for FOL-005. Considering that induction of perifollicular angiogenesis by VEGF is a critical step in activation of the anagen growth phase of hair follicles, we investigated the effect of the more stable FOL-005 analogue FOL-026 on vascular cells.MethodsX-ray diffraction and microscale thermophoresis analysis were used to determine receptor binding of FOL-peptides. Cultured human arterial smooth muscle cells were used for studies of cell proliferation, migration, intracellular signaling, and apoptosis. A Matrigel plug assay was used to study angiogenesis in vivo. RNA seq. was used to analyze changes in gene expression patterns.ResultsFOL-026 was found to share binding site with VEGF in the NRP-1 b1-subdomain. Stimulation of human umbilical vein endothelial cells with FOL-026 resulted in phosphorylation of AKT and ERK1/2, increased cell growth and migration, stimulation of endothelial tube formation and inhibition of apoptosisin vitro,as well as activation of angiogenesisin vivo.Down-regulation of NRP-1 by NRP-1-specific small interfering RNA blocked the stimulatory effects of FOL-026 on endothelial cells. RNA sequencing showed that FOL-026 activated pathways involved in tissue repair. Exposure of human coronary artery smooth muscle cells to FOL-026 stimulated cell proliferation, migration, inhibited apoptosis, and induced VEGF gene expression by an NRP-1-dependent mechanism.ConclusionsThese findings identify NRP-1 as the receptor for FOL-026 and show that its biological effects mimic that of growth factors binding to the VEGF receptor family. They also suggest that FOL-026 may have therapeutical potential in conditions that require vascular repair and / or enhanced angiogenesis.Clinical perspectiveInsufficient vascular repair increases the risk of acute cardiovascular events, something that is of particular importance in diabetes.A peptide derived from the extracellular matrix protein osteopontin (FOL-026) binds to the vascular endothelial growth factor (VEGF) co-receptor neuropilin-1 stimulating endothelial and vascular smooth muscle cell proliferation and migration as well as the formation of new vessels.By mimicking the effects of VEGF FOL-026 may have therapeutical potential in conditions that require vascular repair and / or enhanced angiogenesis such as vascular complications to diabetes, peripheral artery disease and salvage of ischemic myocardium.
Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration
Authors: Pera Edgar M. , Moura Josefine Nilsson-De , Pomeshchik Yuriy , Roybon Laurent , Milas Ivana 
Published: September 2023

ABSTRACTWe previously showed that SerpinE2 and the serine protease HtrA1 modulate fibroblast growth factor (FGF) signaling in germ layer specification and head-to-tail development ofXenopusembryos. Here we present an extracellular proteolytic mechanism involving this serpin-protease system in the developing neural crest (NC). Knockdown of SerpinE2 by injected antisense morpholino oligonucleotides did not affect the specification of NC progenitors but instead inhibited the migration of NC cells, causing defects in dorsal fin, melanocyte and craniofacial cartilage formation. Similarly, overexpression of the HtrA1 protease impaired NC cell migration and the formation of NC-derived structures. The phenotype of SerpinE2 knockdown was overcome by concomitant downregulation of HtrA1, indicating that SerpinE2 stimulates NC migration by inhibiting endogenous HtrA1 activity. SerpinE2 binds to HtrA1, and the HtrA1 protease triggers degradation of the cell surface proteoglycan Syndecan-4 (Sdc4). Microinjection ofSdc4mRNA partially rescued NC migration defects induced both by HtrA1 upregulation and SerpinE2 downregulation. These epistatic experiments suggest a proteolytic pathway by a double inhibition mechanism:SerpinE2 ┤HtrA1 protease ┤Syndecan-4 → NC cell migration
Probucol mitigates high-fat diet-induced cognitive and social impairments through disruption of redox-inflammation association
Authors: Wu Han-Ming , Huang Na-Jun , Yang Yang Vivian , Fan Li-Ping , Tang Tian-Yu , Liu Lin , Xu Yue , Liu Dong-Tai , Cai Ze-Xin , Ren Xin-Yi , Yao Zheng-Hao , Chen Jian-Zhen , Huang Xi , Zhang Cixiong , You Xiang , Wang Chen , He Ying , Ye Zhi-Yun , Hong Wei , Lin Sheng-Cai , Zhan Yi-Hong , Lin Shu-Yong 
Published: September 2023

AbstractObesity and its detrimental metabolic consequences are commonly recognized as risk factors for impairments in the central nervous system (CNS). However, the direct link between metabolic abnormalities and brain functions during high-fat feeding remains unclear. Here, we show that treatment with probucol, a cholesterol-lowering drug, counteracts the cognitive and social impairments induced by a high-fat diet in mice, while having no effect on mood disorders. Unexpectedly, the beneficial effects of probucol do not result from rectifying obesity or restoring glucose and lipid homeostasis, as evidenced by the lack of change in body weight, blood glucose and serum cholesterol levels. Interestingly, high-fat feeding led to association among the levels of redox factors, including oxidized low-density lipoprotein, glutathione and malondialdehyde, as well as a significant negative correlation between malondialdehyde levels and behavioral performance. Probucol treatment interrupts these linkages and differentially regulates the proteins for the generation of reactive oxygen species and reactive nitrogen species in the brain. These findings prompt a reconsideration of the mechanism of action of probucol, as well as the roles of altered metabolic profiles and free radicals in brain function.