bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biophysical modeling identifies an optimal hybrid amoeboid-mesenchymal phenotype for maximal T cell migration speeds
Authors: Alonso-Matilla Roberto , Provenzano Paolo P. , Odde David J. 
Published: November 2023

ABSTRACTDespite recent experimental progress in characterizing cell migration mechanics, our understanding of the mechanisms governing rapid cell movement remains limited. To effectively limit tumor growth, antitumoral T cells need to rapidly migrate to find and kill cancer cells. To investigate the upper limits of cell speed, we developed a new hybrid stochastic-mean field model of bleb-based cell motility. We first examined the potential for adhesion-free bleb-based migration and show that cells migrate inefficiently in the absence of adhesion-based forces, i.e., cell swimming. While no cortical contractility oscillations are needed for cells to swim in viscoelastic media, high-to-low cortical contractility oscillations are necessary for cell swimming in viscous media. This involves a high cortical contractility phase with multiple bleb nucleation events, followed by an intracellular pressure buildup recovery phase at low cortical tensions, resulting in modest net cell motion. However, our model suggests that cells can employ a hybrid bleb- and adhesion-based migration mechanism for rapid cell motility and identifies conditions for optimality. The model provides a momentum-conserving mechanism underlying rapid single-cell migration and identifies factors as design criteria for engineering T cell therapies to improve movement in mechanically complex environments.
Electrophysiological properties of the medial mammillary bodies across the sleep-wake cycle
Authors: Dillingham Christopher M. , Wilson Jonathan J. , Vann Seralynne D. 
Published: November 2023

AbstractThe medial mammillary bodies (MB) play an important role in the formation of spatial memories. Dense anatomical connectivity with hippocampal, brainstem, and thalamic structures, positions them as a focal point for the integration of movement-related and spatial information that is extended to the anterior thalamic nuclei and beyond to cortex. While their anatomical connectivity has been well-studied, much less is known about the physiological properties of the medial MBs, particularly in freely moving animals. We therefore carried out a comprehensive characterization of medial MB electrophysiology across arousal states by concurrently recording from the medial MB and the CA1 field of the hippocampus. In agreement with previous studies, we found medial MB neurons to have firing rates modulated by running speed and angular head velocity, as well as theta-entrained firing. We extended the characterization of MB neuron electrophysiology in three key ways: 1) we identified a subset of neurons (25%) that exhibit dominant bursting activity; 2) we show that ∼30% of theta-entrained neurons exhibit robust theta cycle skipping, a firing characteristic that implicates them in a network for prospective coding of position; 3) A considerable proportion of medial MB units show sharp wave-ripple (SWR) responsive firing (∼37%). The functional heterogeneity of MB electrophysiology reinforces their role as an integrative node for mnemonic processing and identifies potential roles for the MBs in memory consolidation through propagation of SWR-responsive activity to the anterior thalamus and prospective coding in the form of theta-cycle skipping.Significance StatementWhile the medial mammillary bodies (MBs) are important for memory, it is still not clear how they support memory formation. Through conjoint medial MB and hippocampal recordings across different arousal states we identified a population of medial MB units with diverse and often conjunctive physiological properties, including theta-entrained cells, cells modulated by running speed and angular head velocity, complex bursting, theta cycle skipping activity, and hippocampal sharp-wave ripple-responsive firing. These properties likely support a role for the medial MBs in mnemonic processing, enabling the integration of separate sensory streams and the propagation of information to the thalamus.
Adenosine triggers early astrocyte reactivity that provokes microglial activation and drives the pathogenesis of sepsis-associated encephalopathy
Authors: Guo Qilin , Gobbo Davide , Zhao Na , Liu Qing , Fang Li-Pao , Gampfer Tanja M. , Meyer Markus R. , Bai Xianshu , Bian Shan , Scheller Anja , Kirchhoff Frank , Huang Wenhui 
Published: November 2023

SummaryMolecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. Here, we report that in mice during the first 6 hours of peripheral lipopolysaccharide (LPS)-evoked systemic inflammation (6 hpi), the plasma level of adenosine quickly increased and enhanced the tone of central extracellular adenosine which then provoked neuroinflammation by triggering early astrocyte reactivity. Specific ablation of astrocytic A1 adenosine receptors (A1ARs) prevented this early reactivity and reduced the levels of inflammatory factors (e.g., CCL2, CCL5, and CXCL1) in astrocytes, thereby alleviating microglial activation, ameliorating blood-brain barrier disruption, neuronal dysfunction, and depression-like behaviour in the mice. Chemogenetic stimulation of Gi signaling in A1AR-deficent astrocytes at 2 and 4 hpi of LPS injection could restore neuroinflammation and depression-like behaviour, highlighting astrocytes rather than microglia as early drivers of neuroinflammation. Our results identify early astrocyte reactivity towards peripheral and central levels of adenosine as a novel pathway driving SAE.
Efficient semi-supervised semantic segmentation of electron microscopy cancer images with sparse annotations
Authors: Pagano Lucas , Thibault Guillaume , Bousselham Walid , Riesterer Jessica L. , Song Xubo , Gray Joe W. 
Published: November 2023

ABSTRACTElectron microscopy (EM) enables imaging at nanometer resolution and can shed light on how cancer evolves to develop resistance to therapy. Acquiring these images has become a routine task; however, analyzing them is now the bottleneck, as manual structure identification is very time-consuming and can take up to several months for a single sample. Deep learning approaches offer a suitable solution to speed up the analysis. In this work, we present a study of several state-of-the-art deep learning models for the task of segmenting nuclei and nucleoli in volumes from tumor biopsies. We compared previous results obtained with the ResUNet architecture to the more recent UNet++, FracTALResNet, SenFormer, and CEECNet models. In addition, we explored the utilization of unlabeled images through semi-supervised learning with Cross Pseudo Supervision. We have trained and evaluated all of the models on sparse manual labels from three fully annotated in-house datasets that we have made available on demand, demonstrating improvements in terms of 3D Dice score. From the analysis of these results, we drew conclusions on the relative gains of using more complex models, semi-supervised learning as well as next steps for the mitigation of the manual segmentation bottleneck.
Investigating the role of mitochondrial membrane potential in paternal inheritance of mitochondria
Authors: Pouliot-Drouin Ariane , Niaison Thierry , Breton Sophie , Bettinazzi Stefano 
Published: November 2023

AbstractThe process of oxidative phosphorylation (OXPHOS) in mitochondria depends on an electrochemical gradient known as the mitochondrial membrane potential (Δψm). Reflecting high functionality, elevated Δψm usually depicts healthy mitochondria and contribute to organelle selection. This study investigates whether mitochondrial properties linked with bioenergetics, such as Δψm, may play a role in paternal inheritance of mitochondria. More specifically, how sperm Δψm responds to egg chemoattractants in bivalves characterized by distinct mitochondrial inheritance patterns: strict maternal inheritance (SMI) and doubly uniparental inheritance (DUI), the latter displaying sex-specific transmission of paternal mitochondrial DNA (mtDNA). Sperm Δψm was examined in four bivalve species:Mytilus edulisandRuditapes philippinarum(DUI), plusMercenaria mercenariaandMya arenaria(SMI). In absence of oocytes, sperm Δψm did not vary between the two groups. However, we revealed an increase in Δψm following egg detection only in sperm bearing paternally-derived mitochondria (DUI). This suggests, along with bioenergetic changes, that Δψm modulation might be a specific property of DUI paternal mitochondria, possibly implicated in their unique ability to be sex-specifically transmitted.
Metapopulations, the inflationary effect, and consequences for public health
Authors: Kortessis Nicholas , Glass Gregory , Gonzalez Andrew , Ruktanonchai Nick W. , Simon Margaret W. , Singer Burton , Holt Robert D. 
Published: November 2023

AbstractThe metapopulation perspective is an important conceptual framework in ecology and evolutionary ecology. Metapopulations are spatially distributed populations linked by dispersal. Both metapopulation models and their community and ecosystem level analogues, metacommunity and meta-ecosystem models, tend to be more stable regionally than locally and display enhanced abundance because of the interplay of spatiotemporal heterogeneity and dispersal (an effect that has been called the “inflationary effect”). We highlight the essential role of spatiotemporal heterogeneity in metapopulation biology, sketch empirical demonstrations of the inflationary effect, and provide a mechanistic interpretation of how the inflationary effect arises and impacts population growth and abundance. We illustrate the effect with examples from the spread of infectious disease. Namely, failure to recognize the full possible effects of spatiotemporal heterogeneity likely enhanced the spread of COVID-19, a failure based on lack of understanding of emergent population processes at large scales which may hamper control and eradication of other infectious diseases. We finish by noting how the effects of spatiotemporal heterogeneity have implicitly played roles in the history of ecology, ranging across subdisciplines as diverse as natural enemy-victim dynamics, species coexistence, and conservation biology. Seriously confronting the complexity of spatiotemporal heterogeneity could push many of these subdisciplines forward.
Carbonized Tetracycline: a new class of nanomaterial with tuneable antioxidant, reduced cytotoxicity, immunomodulatory, and osteogenic properties
Authors: Mandal Saptarshi , Annamalai Ramkumar T 
Published: November 2023

AbstractTetracycline (TET), a broad-spectrum antibiotic, also possesses different non-antibiotic activities such as inhibition of metalloproteinase (MMP), anti-inflammatory, antioxidant, high bone affinity, etc. However, the comparatively low efficacy of these non-antibiotic properties along with adverse effects such as hyperpigmentation, phototoxicity, long-term skeletal retention, etc. have not helped their broad utilization similar to their use as an antibiotic. In a unique attempt to improve the non-antibiotic properties while reducing the adverse effects, we converted the TET to nano-carbons through partial carbonization. After sorting out two water-dispersible C-TETs (C-TETHT- hydrothermal and C-TETHP- hot plate) based on their improved antioxidant activity, they have been characterized through a host of analytical techniques that showed distinct differences in morphology, size, shape, and surface functionality. Excitingly, the C-TETHTand C-TETHPhave shown differential biological activity in a dosage and time-dependent manner in terms of cytotoxicity, immunomodulation, and osteogenic activity that was found to be associated with their carbonized parameters. Overall, the carbonized nano-drugs, C-TETHTand C-TETHPhave presented substantial early promises on their non-antibiotic properties that could be further explored to develop into some effective therapeutics.
Proteomic insights into the pathophysiology of hypertension-associated albuminuria: Pilot study in a South African cohort
Authors: Govender Melanie A. , Stoychev Stoyan H. , Brandenburg Jean-Tristan , Ramsay Michèle , Fabian June , Govender Ireshyn S. 
Published: November 2023

AbstractBackgroundHypertension is an important public health priority with a high prevalence in Africa. It is also an independent risk factor for kidney outcomes. We aimed to identify potential proteins and pathways involved in hypertension-associated albuminuria by assessing urinary proteomic profiles in black South African participants with combined hypertension and albuminuria compared to those who have neither condition.MethodsThe study included 24 South African cases with both hypertension and albuminuria and 49 control participants who had neither condition. Protein was extracted from urine samples and analysed using ultra-high-performance liquid chromatography coupled with mass spectrometry. Data was generated using data-independent acquisition (DIA) and processed using Spectronaut™ 15. Statistical and functional data annotation were performed on Perseus and Cytoscape to identify and annotate differentially abundant proteins. Machine learning was applied to the dataset using the OmicLearn platform.ResultsOverall, a mean of 1,225 and 915 proteins were quantified in the control and case groups, respectively. Three hundred and thirty-two differentially abundant proteins were constructed into a network. Pathways associated with these differentially abundant proteins included the immune system (q-value [false discovery rate]=1.4×10-45), innate immune system (q=1.1×10-32), extracellular matrix (ECM) organisation (q=0.03) and activation of matrix metalloproteinases (q=0.04). Proteins with high disease scores (76–100% confidence) for both hypertension and CKD included angiotensinogen (AGT), albumin (ALB), apolipoprotein L1 (APOL1), and uromodulin (UMOD). A machine learning approach was able to identify a set of 20 proteins, differentiating between cases and controls.ConclusionsThe urinary proteomic data combined with the machine learning approach was able to classify disease status and identify proteins and pathways associated with hypertension and albuminuria.
Cultivated Robusta coffee meets wildCoffea canephora: Evidence of cultivated-wild hybridisation in the Democratic Republic of the Congo
Authors: Lauren Verleysen , Jonas Depecker , Robrecht Bollen , Justin Asimonyio , Yves Hatangi , Jean-Léon Kambale , Ithe Mwanga Mwanga , Tshimi Ebele , Benoit Dhed’a , Piet Stoffelen , Tom Ruttink , Filip Vandelook , Olivier Honnay 
Published: November 2023

AbstractBackground and aimsPlant breeders are increasingly turning to crop wild relatives (CWRs) to ensure global food security amidst a rapidly changing environment. However, CWR populations are confronted with various human-induced threats, including hybridisation with their nearby cultivated crops, posing a significant threat to the wild gene pool. Here, we focussed on Robusta coffee in the Yangambi region in the DR Congo, where cultivated Robusta coffee coexists with its wild relative (Coffea canephora), creating ample opportunity for genetic exchange. We examined the geographical distribution of cultivated Robusta coffee plants and the incidence of hybridisation between cultivated and wild individuals within the rainforest.MethodsWe used Genotyping-by-Sequencing data from 471 C. canephora individuals across various locations, including natural rainforests, home gardens, and the INERA Coffee Collection, a Robusta coffee field genebank. Our analyses involved establishing robust diagnostic fingerprints that differentiate cultivated from wild coffee, identifying cultivated-wild hybrids and mapping their geographical position.Key resultsWe identified cultivated genotypes and cultivated-wild hybrids in zones with clear anthropogenic activity, and where Robusta coffee cultivated in the home gardens may serve as a source for crop-to-wild gene flow. We found relatively few hybrids and backcrosses in the rainforests, which is so far likely not sufficient for the stable incorporation of alleles from the cultivated gene pool into the CWR gene pool.ConclusionsThe cultivation of Robusta coffee in close proximity to its wild gene pool has led to cultivated genotypes and cultivated-wild hybrids appearing within the natural habitats of C. canephora. Yet, given the high overlap between the cultivated and wild gene pool, together with the relatively low frequency of hybridisation, our results indicate that the overall impact in terms of risk of introgression remains limited so far. Nevertheless, it is important to continue monitoring crop-to-wild gene flow to safeguard the wild gene pool of C. canephora.
Spatio-temporal brain invasion pattern ofStreptococcus pneumoniaeand dynamic changes of the cellular environment in meningitis pathogenesis
Authors: Farmen Kristine , Tofiño-Vian Miguel , Wellfelt Katrin , Olson Lars , Iovino Federico 
Published: November 2023

SummaryStreptococcus pneumoniae(the pneumococcus) is the major cause of bacterial meningitis globally, and pneumococcal meningitis is associated with increased risk of long-term neurological sequelae. These include several sensorimotor functions that are controlled by specific brain regions which, during bacterial meningitis, are damaged by the vast neuroinflammation and bacterial toxins. Little is known about the invasion pattern of the pneumococcus into the brain. Using a bacteremia-derived meningitis mouse model, we combined 3D whole brain imaging with brain microdissection to show that all brain regions were equally affected during disease progression, with pneumococci in close association to the microvasculature. In the hippocampus, the invasion provoked a dynamic microglial response, while the dentate gyrus showed a significant loss of neuroblasts. Our results indicate that, even before symptom occur, the bacterial load throughout the brain causes neuroinflammation and cell death, a pathological scenario which ultimately leads to a failing regeneration of new neurons.
Digitoids: a novel computational platform for mimicking oxygen-dependent firing dynamics inin vitroneuronal networks
Authors: Fabbri Rachele , Ahluwalia Arti , Magliaro Chiara 
Published: November 2023

AbstractIn vitromodels of neural tissues are crucial to gain new insights on the pathophysiology of the brain. However, cell cultures are associated with many drawbacks and difficulties, e.g., technical complexities, ethical problems and high cost. Computational model-based solutions could represent an important tool to support the study of neuron function. In this work we present a novel computational platform where digital neuronal networks, i.e., Digitoids, can be developed with different size and layouts. The Digitoids rely on a novel firing model where the dependence on oxygen concentration is introduced, since it is a crucial limiting factor in cell cultures. To validate the performance of the platform, Digitoids were developed with the same morphological arrangement as observed in neuron monolayersin vitro. The comparison between the functional output of the Digitoids and the experimental data are not statistically different. The platform delivers a flexible digital tool that can easily be adapted for mimickingin vitromodels with increasing complexity and can be exploited to optimize the laboratory experiments involving neuron cultures.Author SummaryThe use of cell models within laboratories is crucial to gain new understandings of the functioning of neuronal assemblies. However, culturing cells requires highly skilled personnel, a huge quantity of disposable materials and is thus associated with elevated costs. To overcome these limitations, the use of computer-based systems that reproduce the electrical behaviour of neurons can be employed. Sincein vitromodels are vessel-free, we present a novel computational model of neuron electrophysiology, where we introduce the dependence on local oxygen concentration Indeed, oxygen affects the metabolism and the function of cultured neurons. Thanks to our model and platform, we are able to reproduce the morphology of the cultured networks of neurons and build the so-calledDigitoids. We then simulate theDigitoidsand obtain their electrophysiological output. We compared theDigitoids’output with experimental data from neurons cultured on microelectrode arrays. We did not find any differences between the electrophysiological output of theDigitoidsand the experimental data, therefore we conclude that our novel oxygen-dependent model can be used to develop more physiologically relevant tools for simulating the activity of cultured neurons.
Sea anemone MACPF proteins demonstrate an evolutionary transitional state between venomous and developmental functions
Authors: Surm Joachim M. , Landau Morani , Columbus-Shenkar Yaara Y. , Moran Yehu 
Published: November 2023

AbstractGene duplication is a major force driving evolutionary innovation. A classic example is generating new animal toxins via duplication of physiological protein-encoding genes and recruitment into venom. While this process drives the innovation of many animal venoms, reverse-recruitment of toxins into non-venomous cells remains unresolved. Using comparative genomics, we find members of the Membrane Attack Complex and Perforin Family (MACPF) have been recruited into venom-injecting cells (cnidocytes), in soft and stony corals and sea anemones, suggesting that the ancestral MACPF was a cnidocyte expressed toxin. Further investigation into the model sea anemoneNematostella vectensis,reveals that three members have undergoneNematostella-specific duplications leading to their reverse-recruitment into mesoendodermal cells. Furthermore, simultaneous knock-down of all three mesoendodermally-expressed MACPFs leads to mis-development, supporting that these paralogs have non-venomous function. By resolving the evolutionary history and function of MACPFs inNematostella, we provide the first proof for reverse-recruitment from venom to organismal development.Significance statementIn this study, we reveal how a gene can gain a new function, even from a most unexpected origin. Specifically, we report that in the last common ancestor of corals and sea anemones a member of the Membrane Attack Complex and Perforin Family (MACPF), which is commonly associated with the immune system, was recruited into venom-injecting cells called cnidocytes. Using the sea anemoneNematostella vectensiswe find repeated gene duplication has occurred leading to the new copies adopting divergent functions including being retained in cnidocytes but also recruited into non-venomous mesoendodermal cells. Furthermore, when we depleteNematostellaof mesoendodermally-expressed MACPFs we disrupt normal embryonic development, supporting that these copies have indeed been recruited from venom into the developmental plan.