bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cleavage of the vascular matrix attracts glioblastoma cells to infiltrate the brain parenchyma
Authors: Perryman Lara , Høye Anette M , Cox Thomas R , Baker Ann-Marie , Strøbech Jan , Leonte Lidia , Singh Lukram B , Popov Sergey , Lorentzen Lasse G , Reuten Raphael , Skovgaard Poulsen Hans , Davies Michael J , Jones Chris , Erler Janine T 
Published: August 2024

AbstractBackgroundGlioblastoma is a highly aggressive brain cancer and, unlike many other cancers types, the median survival for patients after treatment (14.6 months) has barely improved in the last 20 years. Infiltrative growth into the surrounding brain parenchyma facilitates tumor recurrence and ultimately the death of the patient - novel therapies targeting this process are desperately needed. Lysyl oxidase inhibition has been shown to decrease invasive growth in a variety of solid tumours and is a potential therapy for glioblastoma patients.MethodsGenes highly expressed in the mesenchymal subtype of glioblastoma were analyzed in a data set from the Cancer Genome Atlas and tissue microarrays. Two patient-derived human glioblastoma stem cell lines were used to assess the involvement of lysyl oxidase (LOX). The effect of LOX on infiltration was examined in an organotypic brain slice assay and in an orthotopic mouse model. Chemotactic assays, protease and cleavage arrays were used to assess the underlying mechanism behind LOX-mediated infiltration. The orthotopic model was used to evaluate potential clinical utility of targeting LOX in glioblastoma.ResultsLOX is overexpressed in the mesenchymal glioblastoma subtype and strongly associated with poor patient survival. LOX expression upregulates MMP7 expression, which subsequently cleaves the vascular matrix resulting in increased chemotaxis of glioblastoma cells.ConclusionsWe have uncovered a novel mechanism of glioblastoma infiltration and suggest that targeting LOX represent an effective therapeutic approach blocking glioblastoma infiltration.Importance of the studyThe ability of glioblastoma cells to infiltrate the surrounding normal brain tissue facilitates their evasion of current therapies, leading to tumor recurrence and ultimately the death of the patient. To improve targeted therapies for glioblastoma patients we need to understand the molecular mechanisms of glioblastoma cell infiltration and how cells interact with the unique microenvironment of the brain. We have identified a novel mechanism whereby tumor-derived LOX mediates chemotaxis of glioblastoma cells to the laminin rich perivascular niche, enabling infiltrative growth. Inhibiting this infiltrative pathway is a potential anti-invasive therapy that is desperately needed for glioblastoma patients.
Head down tilt 15° increases cerebral perfusion before recanalization in acute ischemic stroke. A pre-clinical MRI study
Authors: Beretta Simone , Carone Davide , Cho Tae-Hee , Viganò Martina , Diamanti Susanna , Mariani Jacopo , Pedrazzini Francesco Andrea , Bianchi Elisa , Pini Cristiano , Bolbos Radu , Wiart Marlene , Ferrarese Carlo , Chauveau Fabien 
Published: August 2024

ABSTRACTWe investigated the therapeutic effect of head down positioning at −15° (head down tilt; HDT15) on cerebral collateral flow and infarct growth in a rat model of large vessel occlusion (LVO) stroke, using multi-modal MRI. Twenty-eight Wistar rats were randomly assigned to HDT15 or flat position for 60 minutes, starting 30 minutes after occlusion of the middle cerebral artery, followed by reperfusion. The perfusion shift analysis, comparing post- versus pre-treatment voxel-level changes in time-to-peak perfusion maps, showed a significant increase in cerebral perfusion in the HDT15 group (common odds ratio 1.50; 95% CI 1.41-1.60; p < 0.0001), but not in the flat group (common odds ratio 0.97; 95% CI 0.92-1.03; p = 0.3503). Infarct growth at 24 hours was + 31.4% in the flat group (343 versus 250 mm3; 95% CI 2.4 to 165.1; p = 0.0447) and + 15.4% in the HDT15 group (224 versus 192 mm3; 95% CI -26.9 to 85.9; p = 0.2272). Our findings indicate that HDT15 acutely increases cerebral perfusion in LVO acute ischemic stroke and provides a tissue-saving effect before recanalization. Further research is needed to develop HDT15 as an emergency therapy to acutely increase collateral flow in ischemic stroke prior to recanalization therapy.
RF Channel-Based Adaptive Beamforming for 3D Ultrasound Localization Microscopy
Authors: Chabouh Georges , Pialot Baptiste , Denis Louise , Dumas Raphael , Couture Olivier , Seya Pauline Muleki , Varray François 
Published: August 2024

ABSTRACTUltrasound Localization Microscopy (ULM) has been applied in various preclinical settings and in the clinic to reveal the microvasculature in deep organs. However, most ULM images employ standard Delay-and-Sum (DAS) beamforming. In standard ULM conditions, lengthy acquisition times are required to fully reconstruct small vessels due to the need for spatially isolated microbubbles, resulting in low temporal resolution. When microbubbles are densely packed, localizing a point spread function with significant main and side lobes becomes challenging due to matrix arrays’ low signal-to-noise ratio and spatial resolution. In this work, we applied adaptive beamforming such as high order DAS known as (pDAS), Coherence Factor (CF), Coherence Factor with Gaussian Filtering (CFGF), and statistical interpretation of beamforming (iMAP) to provide a more complete 3D ULM mapsin vitroandin vivo(rat kidney). Specifically, the CF and 1MAP adaptive beamformers achieved higher resolution (32.9 microns and 27.2 microns respectively), as measured by the Fourier Shell Correlation (FSC), compared to the standard DAS beamformer, which had an FSC value of 38.6 microns.
Conservation of animal genome structure is the exception not the rule
Authors: Lewin Thomas D. , Liao Isabel Jiah-Yih , Luo Yi-Jyun 
Published: August 2024

AbstractSpecies from diverse animal lineages have retained groups of orthologous genes together on the same chromosomes for over half a billion years since their last common ancestor. However, by examining interchromosomal rearrangements across all major bilaterian groups, we show that cases of high-fidelity genome structure conservation are unexpectedly rare. Large-scale genome restructuring events are pervasive, correlate with increased rates of protein sequence evolution, and may contribute to adaptation and animal diversity.
Plectin-mediated cytoskeletal crosstalk as a target for inhibition of hepatocellular carcinoma growth and metastasis
Authors: Outla Zuzana , Oyman-Eyrilmez Gizem , Korelova Katerina , Prechova Magdalena , Frick Lukas , Sarnova Lenka , Bisht Piyush , Novotna Petra , Kosla Jan , Bortel Patricia , Borutzki Yasmin , Bileck Andrea , Gerner Christopher , Rahbari Mohammad , Rahbari Nuh , Birgin Emrullah , Kvasnicova Bibiana , Galisova Andrea , Sulkova Katerina , Bauer Andreas , Jobe Njainday , Tolde Ondrej , Sticova Eva , Rosel Daniel , O’Connor Tracy , Otahal Martin , Jirak Daniel , Heikenwälder Mathias , Wiche Gerhard , Meier-Menches Samuel M. , Gregor Martin 
Published: August 2024

AbstractThe most common primary malignancy of the liver, hepatocellular carcinoma (HCC), is a heterogeneous tumor entity with high metastatic potential and complex pathophysiology. Increasing evidence suggests that tissue mechanics plays a critical role in tumor onset and progression. Here we show that plectin, a major cytoskeletal crosslinker protein, plays a crucial role in mechanical homeostasis and mechanosensitive oncogenic signaling that drives hepatocarcinogenesis. Our expression analyses revealed elevated plectin levels in liver tumors, which correlated with poor prognosis for HCC patients. Using autochthonous and orthotopic mouse models we demonstrated that genetic and pharmacological inactivation of plectin potently suppressed the initiation and growth of HCC. Moreover, plectin targeting potently inhibited the invasion potential of human HCC cells and reduced their metastatic outgrowth in the lung. Proteomic and phosphoproteomic profiling linked plectin-dependent disruption of cytoskeletal networks to attenuation of oncogenic FAK, MAPK/Erk, and PI3K/AKT signatures. Importantly, by combining cell line-based and murine HCC models, we show that plectin inhibitor plecstatin-1 (PST) is well-tolerated and potently inhibits HCC progression. In conclusion, our study demonstrates that plectin-controlled cytoarchitecture is a key determinant of HCC development and suggests that pharmacologically induced disruption of mechanical homeostasis may represent a new therapeutic strategy for HCC treatment.
Monitoring free-living honeybee colonies in Germany: Insights into habitat preferences, survival rates, and Citizen Science reliability
Authors: Rutschmann Benjamin , Remter Felix , Roth Sebastian 
Published: August 2024

ABSTRACTOur understanding of the western honeybee (Apis mellifera) predominantly stems from studies conducted within beekeeping environments, leaving the presence and characteristics of honeybees outside managed settings largely unexplored. This study examined the habitats, nesting sites, and survival rates of free-living colonies through personal monitoring of nest sites in Munich (N=107) and the coordination of Citizen Science monitoring across Germany (N=423). Within seven years we collected 2,555 observations on 530 colonies from 311 participants. Nesting preferences differed between urban, rural, and forested areas. Overall, we found that 31% of the occupied nest sites were in buildings and 63% in mature trees, with clear preferences for specific tree species. On average, only 12% of the personal monitored colonies in Munich survived annually, a figure that aligns well with other published studies but contrasts sharply with the significantly higher survival rates reported by Citizen Science (29%). We found that Citizen Science yielded significantly fewer updates per colony, underreported abandoned sites, and that 46% of overwintering reports overlapped with the swarming season and had to be excluded. To gain reliable survival data in Citizen Science projects, consistency and timing of reports need particular attention and regional swarming should be monitored too. This study enhances our understanding of the ecological dynamics, liminal state, and conservation needs of free-living honeybee cohorts, addresses potential monitoring biases, and suggests standardized data collection protocols for future monitoring projects.
Molecular hydrogen can minimize negative effects of heat stress on the hard coral genusAcropora
Authors: Ostendarp Malte , de Breuyn Mareike , El-Khaled Yusuf C. , Garcias-Bonet Neus , Carvalho Susana , Peixoto Raquel S. , Wild Christian 
Published: August 2024

AbstractCoral reefs are increasingly threatened by mass bleaching events due to global ocean warming. Novel management strategies are urgently needed to support coral survival until global efforts can mitigate ocean warming. Given the strong antioxidant, anti-inflammatory and anti-apoptotic properties of molecular hydrogen, our study explores its potential to alleviate the negative effects of heat stress on corals. We investigated the ecophysiological responses of two common hard corals (Acroporaspp. andPocillopora verrucosa) from the Central Red Sea under ambient (26 °C) and elevated seawater temperatures (32 °C), with and without hydrogen addition (∼ 150 µM H2) over 48 h. Our results showed that at 32 °C without hydrogen addition,P. verrucosaexhibited high temperature tolerance, whereasAcroporaspp. showed significant reductions in photosynthetic efficiency and maximum electron transport rate compared to the ambient condition (26 °C). The addition of hydrogen at 32 °C increased the maximum electron transport rate ofAcroporaspp. by 28 %, maintaining it at levels compared to those at 26 ° C. This suggests that molecular hydrogen benefits specific coral species under heat stress in the short-term. This study provides the foundation for future long-term and in-situ studies, potentially guiding the development of new management strategies aiming at enhancing coral resilience to ocean warming.
Resting-state causal brain connectivity in youth female athletes suggest sex-related differences following subacute concussion
Authors: McLeod Julianne , Sattari Sahar , Hristopulos Dionissios T. , Thanjavur Karun , Virji-Babul Naznin 
Published: August 2024

AbstractObjectiveYouth male athletes show changes in resting-state causal brain connectivity following subacute concussion; however, little is known about how concussion alters causal brain connectivity in female youth. In this study, we compared resting-state causal brain connectivity in healthy and subconcussed females.Materials and methodsData from 11 concussed and 15 healthy control female athletes were included in this study. Five minutes of resting state eyes-closed EEG data were collected from all participants. SCAT5 data were also collected from all concussed participants. Causal connectivity was calculated from EEG source data. Network topology was evaluated using the degree assortativity coefficient, a summary statistic describing network structure of information flow between source locations.ResultsWe observed three main results: 1) a qualitative difference in the spatial pattern of the most active connections, marked by posterior connectivity shifting in the concussed group, 2) an increase in the magnitude of connectivity in the concussed group, and 3) no significant difference in degree assortativity between the concussed and control groups.ConclusionCausal connectivity changes following concussion in females do not follow the same trends reported in males. These findings suggest a potential sex difference in injury response and may have implications for recovery.
Individual alpha frequency tACS reduces functional connectivity across the default mode network
Authors: Carrasco-Gómez Martín , García-Colomo Alejandra , Cabrera-Álvarez Jesús , del Cerro-León Alberto , Gómez-Ariza Carlos J. , Santos Andrés , Maestú Fernando 
Published: August 2024

Structured AbstractObjectivesResearch on the influence of transcranial alternating current stimulation over alpha functional connectivity (FC) is scarce, and at the same time poses as a potential treatment for various diseases. This study aimed to investigate the effects of individualized alpha frequency tACS (IAF-tACS) on FC within the default mode network (DMN) in healthy individuals, particularly focusing on the precuneus (PCU) as a major hub within the network.Materials and Methods27 healthy participants were recruited, which underwent a 20-minute IAF-tACS session and three magnetoencephalography (MEG) recordings: two pre-stimulation and one post-stimulation. Participants were randomly assigned to either the stimulation or sham group. FC was evaluated through the corrected imaginary phase locking value (ci-PLV) and leakage corrected amplitude envelope correlation (AEC-c). Statistical analyses compared both Pre-Post FC ratio between groups through ratio t-tests and intragroup FC changes through repeated measures t-tests, with FDR correction applied to account for multiple comparisons. An additional analysis simulated the influence of the cortical folding on the effect of tACS over FC.ResultsIAF-tACS significantly decreased AEC-c within the PCU and DMN in the stimulation group compared to the sham group, especially influencing antero-posterior links between hubs of the DMN. No significant changes were observed in ci-PLV connectivity metrics. Negative correlations were found between AEC-c FC changes and power alterations in posterior DMN areas, suggesting a complex interaction between cortical folding and electric field direction.ConclusionsAgainst our initial hypothesis, IAF-tACS reduced FC in the DMN, possibly due to phase disparities introduced by cortical gyrification. These findings suggest that tACS might modulate FC in a more complex manner than previously thought, highlighting the need for further research into the personalized application of neuromodulation techniques, as well as its potential therapeutic implications for conditions like Alzheimer’s disease.
Effects of Aging, Fitness, and Cerebrovascular Status on White Matter Microstructural Health
Authors: Clements Grace M. , Camacho Paul , Bowie Daniel C. , Low Kathy A. , Sutton Bradley P. , Gratton Gabriele , Fabiani Monica 
Published: August 2024

AbstractWhite matter (WM) microstructural health declines with increasing age, with evidence suggesting that improved cardiorespiratory fitness (CRF) may mitigate this decline. Specifically, higher fit older adults tend to show preserved WM microstructural integrity compared to their lower fit counterparts. However, the extent to which fitness and agingindependentlyimpact WM integrity across the adult lifespan is still an open question, as is the extent to which cerebrovascular health mediates these relationships. In a large sample (N = 125, aged 25-72), we assessed the impact of age and fitness on fractional anisotropy (FA, derived using diffusion weighted imaging, DWI) and probed the mediating role of cerebrovascular health (derived using diffuse optical tomography of the cerebral arterial pulse, pulse-DOT) in these relationships. After orthogonalizing age and fitness and computing a PCA on whole brain WM regions, we found several WM regions impacted by age that were independent from the regions impacted by fitness (hindbrain areas, including brainstem and cerebellar tracts), whereas other areas showed interactive effects of age and fitness (midline areas, including fornix and corpus callosum). Critically, cerebrovascular health mediatedbothrelationships suggesting that vascular health plays a linking role between age, fitness, and brain health. Secondarily, we assessed potential sex differences in these relationships and found that, although females and males generally showed the same age-related FA declines, males exhibited somewhat steeper declines than females. Together, these results suggest that age and fitness impact specific WM regions and highlight the mediating role of cerebrovascular health in maintaining WM health across adulthood.
The Dichoptic Contrast Ordering Test: A method for measuring the depth of binocular imbalance
Authors: Baldwin Alex S , Lorenzini Marie-Céline , Fan Annabel Wing-Yan , Hess Robert F , Reynaud Alexandre 
Published: August 2024

AbstractIn binocular vision, the relative strength of the input from the two eyes can have significant functional impact. These inputs are typically balanced, however in some conditions (e.g. amblyopia) one eye will dominate over the other. To quantify imbalances in binocular vision, we have developed the Dichoptic Contrast Ordering Test (DiCOT). Implemented on a tablet device, the program uses rankings of perceived contrast (of dichoptically-presented stimuli) to find a scaling factor that balances the two eyes. We measured how physical interventions (applied to one eye) affect the DiCOT measurement. These were: i) neutral density filters, ii) Bangerter filters, and iii) optical blur introduced by a +3 D lens. The DiCOT results were compared to those from the Dichoptic Letter Test (DLT). Both the DiCOT and the DLT showed excellent test-retest reliability, however the magnitude of the imbalances introduced by the interventions was greater in the DLT. To find consistency between the methods, rescaling the DiCOT results from individual conditions gave good results. However, the adjustments needed for the +3 D lens condition were quite different from those for the ND and Bangerter filter. Our results indicate that the DiCOT and DLT measure partially separate aspects of binocular imbalance. This supports the simultaneous use of both measures in future studies.
Resting-State EEG Reveals Regional Brain Activity Correlates in Alzheimer’s and Frontotemporal Dementia
Authors: Azargoonjahromi Ali , Nasiri Hamide , Abutalebian Fatemeh 
Published: August 2024

AbstractResting-state EEG records brain activity when awake but not engaged in tasks, analyzing frequency bands linked to cognitive states. Recent studies on Alzheimer’s disease (AD) and frontotemporal dementia (FTD) have found a link between EEG activity, MMSE scores, and age, though some findings are conflicting. This study aimed to explore EEG regional differences among AD and FTD, thereby improving diagnostic strategies. We analyzed EEG recordings from 88 participants in OpenNeuro Dataset ds004504, collected at AHEPA General Hospital using a Nihon Kohden 2100 EEG device. The study used preprocessed recordings, classification algorithms, and cognitive function assessments (MMSE) to identify significant predictors and correlations between EEG measures and cognitive variables. The study revealed that cognitive function, age, and brain activity show distinct relationships in AD and FTD. In AD, MMSE scores significantly predicted brain activity in regions like C3, C4, T4, and Fz, with better cognitive performance linked to higher EEG power in frontal and temporal areas. Conversely, age had a major influence on brain activity in FTD, particularly in regions like C3, P3, O1, and O2, while MMSE scores did not significantly predict brain activity. In FTD, higher EEG power in regions like P3, P4, Cz, and Pz correlated with lower cognitive function. Thus, the findings suggest that EEG biomarkers can enhance diagnostic strategies by highlighting different patterns of brain activity related to cognitive function and age in AD and FTD.
The molecular basis of lamin-specific chromatin interactions
Authors: Wang Baihui , Kronenberg-Tenga Rafael , Rosti Valentina , Di Patrizio Soldateschi Emanuele , Luo Qiang , Pinet Louise , Eibauer Matthias , Boujemaa-Paterski Rajaa , Schuler Benjamin , Lanzuolo Chiara , Medalia Ohad 
Published: August 2024

AbstractIn the cell nucleus, chromatin is anchored to the nuclear lamina, a network of lamin filaments and binding proteins that underly the inner nuclear membrane. The nuclear lamina is involved in chromatin organisation through the interaction of lamina-associated domains (LADs) within the densely packed heterochromatin regions. Employing cryo-focused ion beam (cryo-FIB) milling in conjunction with cryo-electron tomography (cryo-ET), we analysed the distribution of nucleosomes at the lamin-chromatin interface. Depletion of lamin A/C reduced the concentration of nucleosomes at the nuclear periphery, suggesting that lamins are directly involved in the interaction with chromatin. Using cryo-electron microscopy (cryo-EM), we then identified the specific binding motif of the lamin A tail domain that interacts with nucleosomes, distinguishing it from the other lamin isoforms. Furthermore, we examined chromatin structure dynamics using a genome-wide analysis that revealed lamin-dependent macroscopic-scale alterations in gene expression and chromatin remodelling. Our findings provide detailed insights into the dynamic and structural interplay between lamin isoforms and chromatin, molecular interactions which are shaping chromatin architecture and epigenetic regulation.