bluuebunny/crossref_metadata_2025_split huggingface dataset:
niiv: Fast Self-supervised Neural Implicit Isotropic Volume Reconstruction
Authors: Troidl Jakob , Liang Yiqing , Beyer Johanna , Tavakoli Mojtaba , Danzl Johann , Hadwiger Markus , Pfister Hanspeter , Tompkin James 
Published: September 2024

AbstractThree-dimensional (3D) microscopy data often is anisotropic with significantly lower resolution (up to 8×) along thezaxis than along thexyaxes. Computationally generating plausible isotropic resolution from anisotropic imaging data would benefit the visual analysis of large-scale volumes. This paper proposesniiv, a self-supervised method for isotropic reconstruction of 3D microscopy data that can quickly produce images at arbitrary (continuous) output resolutions. Within a neural field, the representation embeds a learned latent code that describes the implicit higher-resolution isotropic image region. Under isotropic volume assumptions, we self-supervise this representation on low-/high-resolution lateral image pairs to reconstruct an isotropic volume from low-resolution axial images. We evaluate our method on simulated and real anisotropic electron (EM) and light microscopy (LM) data. Compared to a state-of-the-art diffusion-based method,niivshows improved reconstruction quality (+1 dB PSNR) and is over three orders of magnitude faster (2,000×) to infer. Specifically,niivreconstructs a 1283voxel volume in 1/10th of a second, renderable at varying (continuous) high resolutions for display.
Advanced Tissue Technologies of Blood-Brain Barrier Organoids as High Throughput Toxicity Readouts in Drug Development
Authors: Bell Luisa , Simonneau Claire , Zanini Chiara , Kassianidou Elena , Zundel Christelle , Neff Rachel , Steinhuber Bernd , Tecilla Marco , Odermatt Alex , Villaseñor Roberto , Stokar-Regenscheit Nadine 
Published: September 2024

SummaryRecent advancements in engineering Complexin vitromodels (CIVMs) such as Blood-brain barrier (BBB) organoids offer promising platforms for preclinical drug testing. However, their application in drug development, and especially for the regulatory purposes of toxicity assessment, requires robust and reproducible techniques. Here, we developed an adapted set of orthogonal image-based tissue methods including hematoxylin and eosin staining (HE), immunohistochemistry (IHC), multiplex immunofluorescence (mIF), and Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) to validate CIVMs for drug toxicity assessments. We developed an artificial intelligence (AI) algorithm to increase the throughput and the reliability of histomorphologic evaluations of apoptosis forin vitrotoxicity studies. Our data highlight the potential to integrate advanced morphology-based readouts such as histological techniques and digital pathology algorithms for use on CIVMs, as part of a standard preclinical drug development assessment.Graphical abstractThe graphical abstract was partially created with biorender.com.HighlightsAdvanced Complexin vitromodels (CIVMs) like Blood-brain barrier (BBB) organoids show promise for preclinical drug testing. However, robust and reproducible techniques are crucial for the acceptance of CIVMs in drug development processes, especially for toxicity assessments which are highly regulated by health authorities.We developed orthogonal image-based readouts on histological sections to enable the use of BBB organoids for future compound toxicity assessment.A newly established artificial intelligence (AI) algorithm provides automated and label-free detection of apoptotic cells in drug screening using BBB organoids and provides an alternative killing assay on single cell resolution (40×) to current standards.
Multiplexing of functionally distinct inputs by intrinsic modulation of spike timing in a monoaminergic nucleus
Authors: Lynn Michael , Maler Leonard , Béïque Jean-Claude 
Published: September 2024

AbstractMonoaminergic nuclei such as the serotonergic dorsal raphe nucleus (DRN) receive synaptic inputs containing functionally distinct streams of information, yet the dimensionality of the resulting output population code and its cellular underpinning are currently unknown. By combining electrophysiological and computational approaches, here we uncover separable neural encoding of two excitatory inputs conveying disjunct information to DRN 5-HT neurons - the lateral habenula (LHb) and medial prefrontal cortex (mPFC). Dual-color opsin strategies revealed that a population of 5-HT neurons receive inputs from both mPFC and LHb. Subthreshold excitatory postsynaptic potentials triggered by both inputs were largely indistinguishable, yet suprathreshold spiking behavior exhibited input-specific latencies and dispersion statistics. A support vector machine classifier demonstrated that input identity can be accurately decoded from spike timing, but not subthreshold events, of under ten 5-HT neurons. Upon examining the intrinsic cellular mechanisms in 5-HT neurons that couple EPSPs to spiking dynamics, we uncovered two likely candidate mechanisms: a low-threshold calcium conductance that selectively boosts slow excitatory inputs, and a subthreshold, voltage-dependent membrane noise that generates variation of spike latency and jitter. Stochastic simulations suggest that these two intrinsic properties of 5-HT neurons are sufficient to transform LHb and mPFC inputs into distinct output spiking patterns. These results reveal that hub-like networks like the DRN can segregate distinct informational streams by a cell-intrinsic mechanism. The resulting emergent population spike synchrony code provides a means for the DRN to widely broadcast these streams as a multiplexed signal.Significance statementPhylogenetically old neuromodulatory systems in the brain, such as the serotonergic dorsal raphe nucleus, are compact yet richly innervated structures. Here, we use the raphe as a testbed to ask how distinct informational sources to hub-like networks are processed or integrated into a coherent neural code. Using electrophysiological and computational methods, including biophysically grounded stochastic simulations, we find that intrinsic noise mechanisms in serotonergic neurons are critical to transform approximately matched subthreshold excitation into distinct spike timing profiles. Thus, cell-intrinsic noise mechanisms can effectively synthesize a spike synchrony code that, we hypothesize, multiplexes input information to hub-like networks at the population level even in the absence of strong local circuit interactions.
Environment-mediated interactions cause an externalized and collective memory in microbes
Authors: Gajrani Shubham , Ye Xiaozhou , Ratzke Christoph 
Published: September 2024

AbstractMicrobes usually live in complex communities interacting with many other microbial species. These interactions determine who can persist in a community and how the overall community forms and functions. Microbes often exert interactions by chemically changing the environment, like taking up nutrients or producing toxins. These environmental changes can persist over time. We show here that such lasting environmental changes can cause a memory effect where current growth conditions alter interaction outcomes in the future. Importantly, this memory is only stored in the environment and not inside the bacterial cells. Only the collective effort of many bacteria can build up this memory, making it an emergent property of bacterial populations. This “population memory” can also impact the assembly of more complex communities and lead to different final communities depending on the system’s past. Overall, we show that to understand interaction outcomes fully, we not only have to consider the interacting species and abiotic conditions but also the system’s history.
Targets of influenza Human T cell response are mostly conserved in H5N1
Authors: Sidney John , Kim A-Reum , de Vries Rory D. , Peters Bjoern , Meade Philip S. , Krammer Florian , Grifoni Alba , Sette Alessandro 
Published: September 2024

SummaryFrequent recent spillovers of subtype H5N1 clade 2.3.4.4b highly pathogenic avian influenza (HPAI) virus into poultry and mammals, especially dairy cattle, including several human cases, increased concerns over a possible future pandemic. Here, we performed an analysis of epitope data curated in the Immune Epitope Database (IEDB). We found that the patterns of immunodominance of seasonal influenza viruses circulating in humans and H5N1 are similar. We further conclude that a significant fraction of the T cell epitopes is conserved at a level associated with cross-reactivity between avian and seasonal sequences, and we further experimentally demonstrate extensive cross-reactivity in the most dominant T cell epitopes curated in the IEDB. Based on these observations, and the overall similarity of the neuraminidase (NA) N1 subtype encoded in both HPAI and seasonal H1N1 influenza virus as well as cross-reactive group 1 HA stalk-reactive antibodies, we expect that a degree of pre-existing immunity is present in the general human population that could blunt the severity of human H5N1 infections.
Ultrastructural analysis of the brain endothelium by electron tomography
Authors: Kotchetkov Pavel , Lacoste Baptiste 
Published: September 2024

AbstractTransmission electron microscopy (TEM) is a powerful imaging technique, yielding ultrastructural investigation of organic and non-organic samples. Despite its ability to reach nanoscale resolutions, conventional TEM presents a major disadvantage by only acquiring two-dimensional snapshots, thus hindering our volumetric understanding of samples. Electron tomography (ET) overcomes this limitation by offering detailed views of a thin specimen in 3 dimensions (3D). This technique is widely used in biology and has expanded our understanding of mitochondrial structure or synaptic organization. Proper brain functioning is highly reliable on a constant nutritional support through its microvasculature lined by endothelial cells. These unique cells form a selective and protective barrier, known as the blood-brain barrier (BBB), which limits the entrance of blood-borne molecules into the brain. In pathological conditions, the BBB is disrupted, resulting in neuronal damage. Understanding the fine changes underlying BBB disruption requires advanced imaging tools such as ET, to detect the finest changes in endothelial ultrastructure. This manuscript briefly explains how TEM and ET function, and then provides a detailed, didactic method for sample preparation, tomogram generation and 3D segmentation of brain endothelial cells using ET.
The level of endothelial glycocalyx maturity modulates interactions with charged nanomaterials
Authors: Bridges Claire A. , Fu Lu , Yeow Jonathan , Huang Xiaojing , Jackson Miriam , Kuchel Rhiannon P. , Sterling James D. , Baker Shenda M. , Lord Megan S. 
Published: September 2024

AbstractNanomaterials have been extensively investigated for their potential in delivering therapeutics to target tissues, but few have advanced to clinical application. The luminal surface of endothelial cells that line blood vessels are covered by a glycocalyx, a complex extracellular matrix rich in anionic glycans. However, the role of this glycocalyx in governing nanomaterial-cell interactions is often overlooked. In this study, we demonstrate that gold nanoparticles functionalized with branched polyethyleneimine (AuNP+) bind to primary human endothelial cells expressing either a developing or mature glycocalyx, with the interaction involving hyaluronan and heparan sulfate. Notably, the mature glycocalyx decreases the toxicity of AuNP+. In contrast, lipoic acid-functionalized gold nanoparticles (AuNP-) bind to endothelial cells with a developing glycocalyx, but not a mature glycocalyx. To further investigate this phenomenon, we studied charged polymers, including poly(arginine) (polyR) and poly(glutamic acid) (polyE). PolyE does not associate with endothelial cells regardless of glycocalyx maturity, but when glycans are enzymatically degraded, it can bind to the cells. Conversely, polyR associates with endothelial cells irrespective of glycocalyx maturity or glycan degradation. These findings highlight the intricate relationship between nanomaterial charge and presentation in interactions with endothelial cells, offering insights for modulating nanomaterial interactions with the blood vessel wall.
How does co-occurrence ofDaphniaspecies affect their gut microbiome?
Authors: Houwenhuyse Shira , Massol Francois , Macke Emilie , De Meester Luc , Vanoverberghe Isabel , Stoks Robby , Decaestecker Ellen 
Published: September 2024

AbstractSpecies co-occurrence can lead to competitive interactions that influence fitness. Competition is typically assumed to be modulated by species niche, especially food–acquisition related traits. The influence of interspecific interactions on host microbiome communities has rarely been considered, and yet may provide an alternative mechanism regarding the effect of host species co-occurrence on their fitness. Here, we investigated whether the composition of the gut microbial community differs between twoDaphniaspecies (D. magnaandD. pulex), and whether the gut microbiome of one species depends on the presence of the other. We hypothesized the stronger filter-feederD. magnato have a larger effect on the gut microbiome of the weaker filter-feederD. pulexthanvice versa. To this purpose, threeD. magnaand threeD. pulexgenotypes were first made axenic and then grown in monocultures or in cocultures in natural environmental bacterioplankton-enriched water, before assessing the community composition of the gut microbiomes and bacterioplankton. We found that the composition of the gut microbiome of the twoDaphniaspecies did not significantly differ overall. However, subtle differences between mono- and cocultures were found at theDaphniagenotype level. For most genotype combinations (six out of nine), the microbiome ofD. pulexchanged more when grown in cocultures withD. magnathan in monocultures. This provides limited support for our hypothesis that the stronger competitor has a larger effect on the gut microbiome of the weaker one thanvice versa, and that this effect is possibly mediated via the bacterioplankton community.
Predicting Task Activation Maps from Resting-State Functional Connectivity using Deep Learning
Authors: Madsen Soren J. , Uddin Lucina Q. , Mumford Jeanette A. , Barch Deanna M. , Fair Damien A. , Gotlib Ian H. , Poldrack Russell A. , Kuceyeski Amy , Saggar Manish 
Published: September 2024

AbstractRecent work has shown that deep learning is a powerful tool for predicting brain activation patterns evoked through various tasks using resting state features. We replicate and improve upon this recent work to introduce two models, BrainSERF and BrainSurfGCN, that perform at least as well as the state-of-the-art while greatly reducing memory and computational footprints. Our performance analysis observed that low predictability was associated with a possible lack of task engagement derived from behavioral performance. Furthermore, a deficiency in model performance was also observed for closely matched task contrasts, likely due to high individual variability confirmed by low test-retest reliability. Overall, we successfully replicate recently developed deep learning architecture and provide scalable models for further research.
Anisotropy of object nonrigidity: High-level perceptual consequences of cortical anisotropy
Authors: Maruya Akihito , Zaidi Qasim 
Published: September 2024

AbstractWe demonstrate an unexpected anisotropy in perceived object non-rigidity, a higher-level perceptual phenomenon, and explain it by the population distribution of low-level neuronal properties in primary visual cortex. We measured the visual interpretation of two rigidly connected rotating circular rings. In videos where observers predominantly perceived rigidly-connected horizontally rotating rings, they predominantly perceived non-rigid independently wobbling rings if the video was rotated by 90°. Additionally, vertically rotating rings appeared narrower and longer than horizontally rotating counterparts. We decoded these perceived shape changes from V1 outputs incorporating documented cortical anisotropies in orientation selectivity: more cells and narrower tuning for the horizontal orientation than for vertical. Even when shapes were matched, the non-rigidity anisotropy persisted, suggesting uneven distributions of motion-direction mechanisms. When cortical anisotropies were incorporated into optic flow computations, the kinematic gradients (Divergence, Curl, Deformation) for vertical rotations aligned more with derived gradients for physical non-rigidity, while those for horizontal rotations aligned closer to rigidity. Our results reveal how high-level non-rigidity percepts can be shaped by hardwired cortical anisotropies. Cortical anisotropies are claimed to promote efficient encoding of statistical properties of natural images, but their surprising contribution to failures of shape constancy and object rigidity raise questions about their evolutionary function.
Interpreting prediction intervals and distributions for decoding biological generality in meta-analyses
Authors: Yang Yefeng , Noble Daniel W. A. , Senior Alistair M. , Lagisz Malgorzata , Nakagawa Shinichi 
Published: September 2024

AbstractDespite the importance of identifying predictable regularities for knowledge transfer across contexts, the generality of ecological and evolutionary findings is yet to be systematically quantified. We present the first large-scale evaluation of generality using new metrics. By focusing on biologically relevant study levels, we show that generalization is not uncommon. Overall, 20% of meta-analyses will produce a non-zero effect 95% of the time in future replication studies with a 70% probability of observing meaningful effects in study-level contexts. We argue that the misconception that generalization is exceedingly rare is due to conflating within-study and between-study variances in ecological and evolutionary meta-analyses, which results from focusing too much on total heterogeneity (the sum of within-study and between-study variances). We encourage using our proposed approach to elucidate general patterns underpinning ecological and evolutionary phenomena.
AI-generated small binder improves prime editing
Authors: Park Ju-Chan , Uhm Heesoo , Kim Yong-Woo , Oh Ye Eun , Bae Sangsu 
Published: September 2024

AbstractThe prime editing 2 (PE2) system comprises a nickase Cas9 fused to a reverse transcriptase utilizing a prime editing guide RNA (pegRNA) to introduce desired mutations at target genomic sites. However, the PE efficiency is limited by mismatch repair (MMR) that excises the DNA strand containing desired edits. Thus, inhibiting key components of MMR complex through transient expression of a dominant negative MLH1 (MLH1dn) exhibited approximately 7.7-fold increase in PE efficiency over PE2, generating PE4. Herein, by utilizing a generative artificial intelligence (AI) technologies, RFdiffusion and AlphaFold 3, we ultimately generated a de novo MLH1 small binder (named MLH1-SB), which bind to the dimeric interface of MLH1 and PMS2 to disrupt the formation of key MMR components. MLH1-SB’s small size (82 amino acids) allowed it to be integrated into pre-existing PE architectures via the 2A system, creating a novel PE-SB platform. Resultantly, by incorporating MLH1-SB into PE7, we have developed an improved PE architecture called PE7-SB, which demonstrates the highest PE efficiency to date (29.4-fold over PE2 and 2.4-fold over PE7 in HeLa cells), providing an insight that generative AI technologies will boost up the improvement of genome editing tools.
Pathogenic microbiota disrupts the intact structure of cerebral organoids by altering energy metabolism
Authors: Isik Melis , Eylem Cemil Can , Erdogan-Gover Kubra , Aytar-Celik Pinar , Enuh Blaise Manga , Emregul Emel , Cabuk Ahmet , Yildirim Yalin , Nemutlu Emirhan , Muotri Alysson Renato , Derkus Burak 
Published: September 2024

ABSTRACTThis study investigated the impact of different bacterial populations on the biomolecular structures of cerebral organoids (COs) at various levels. COs were co-cultured with non-pathogenic (NM) and pathogenic (PM) bacterial populations. PM reduced the number of TUJ1+ neurons and disrupted the intact structure of COs. In addition, PM was found to induce changes in the transcript profile of COs, including a decrease in the activity of the glycolysis pathway and an increase in the pentose phosphate pathway, leading to deterioration in cellular energy metabolism, which is linked to neurodegenerative diseases. Proteomic analysis revealed a unique cluster of proteins in COs. PM exposure upregulated proteins related to neurological diseases, consistent with RNA-seq data. Communication between bacteria and neural cells was demonstrated using18O-stable isotope labeling (SIL)-based metabolic flux analysis. COs showed higher18O-enrichment of TCA cycle intermediates when co-cultured with NM and PM, indicating increased oxidative phosphorylation activity upon exposure to bacteria. This study provides a useful platform to monitor metabolic signals and communication between microbiotas and human brain cells. The findings suggest that pathogenic bacteria release metabolites that alter biomolecular structures in brain organoids, potentially contributing to neurodegenerative diseases.
Retinoic acid-mediated homeostatic plasticity drives cell type-specific CP-AMPAR accumulation in nucleus accumbens core and incubation of cocaine craving
Authors: Hwang Eun-Kyung , Wunsch Amanda M. , Wolf Marina E. 
Published: September 2024

AbstractIncubation of cocaine craving, a translationally relevant model for the persistence of drug craving during abstinence, ultimately depends on strengthening of nucleus accumbens core (NAcc) synapses through synaptic insertion of homomeric GluA1 Ca2+-permeable AMPA receptors (CP-AMPARs). Here we tested the hypothesis that CP-AMPAR upregulation results from a form of homeostatic plasticity, previously characterized in vitro and in other brain regions, that depends on retinoic acid (RA) signaling in dendrites. Under normal conditions, ongoing synaptic transmission maintains intracellular Ca2+at levels sufficient to suppress RA synthesis. Prolonged blockade of neuronal activity results in disinhibition of RA synthesis, leading to increased GluA1 translation and synaptic insertion of homomeric GluA1 CP-AMPARs. Using slice recordings, we found that increasing RA signaling in NAcc medium spiny neurons (MSN) from drug-naïve rats rapidly upregulates CP-AMPARs, and that this pathway is operative only in MSN expressing the D1 dopamine receptor. In MSN recorded from rats that have undergone incubation of craving, this effect of RA is occluded; instead, interruption of RA signaling in the slice normalizes the incubation-associated elevation of synaptic CP-AMPARs. Paralleling this in vitro finding, interruption of RA signaling in the NAcc of ‘incubated rats’ normalizes the incubation-associated elevation of cue-induced cocaine seeking. These results suggest that RA signaling becomes tonically active in the NAcc during cocaine withdrawal and, by maintaining elevated CP-AMPAR levels, contributes to the incubation of cocaine craving.