bluuebunny/crossref_metadata_2025_split huggingface dataset:
The assembly of cancer-specific ribosomes by the lncRNALISRRsuppresses melanoma anti-tumour immunity
Authors: Cinque Sonia , Verheyden Yvessa , Adnane Sara , Marino Alessandro , Katopodi Vicky , Demesmaeker Ewout , Knezevic Zorica , Hanache Sarah , Vendramin Roberto , Cuomo Alessandro , Pozniak Joanna , Calabuig Alvaro Cortes , Baldewijns Marcella , Tabruyn Sébastien , Bechter Oliver , Baietti Maria Francesca , Groaz Elisabetta , Bonaldi Tiziana , Leucci Eleonora 
Published: January 2023

AbstractAlthough immune checkpoint blockade (ICB) has revolutionized cancer treatment, resistance mechanisms limit its clinical benefit. Here we characteriseLISRR, a cancer-specific lncRNA highly expressed in melanoma patients refractory to ICB. In cells undergoing (therapeutic) stress,LISRRrecruits DAZAP1 (Deleted in AZoospermia Associated Protein 1) to polysomes and drives the assembly of a subset of ribosomes at the endoplasmic reticulum, directing the synthesis of an immunosuppressive translatome. This includes the immune checkpoint PD-L1 and the enzymes necessary for building the glycocalyx, the sugar coat surrounding the cells. Notably, proper glycocalyx assembly is required for spermatozoa immune evasion during fertilization. Accordingly, targetingLISRRactivates immune responses and re-sensitizes to ICB in co-culture models,ex vivoin patient explants, andin vivoin humanized patient-derived models. Our study reveals the contribution of lncRNAs to the generation of cancer-specific ribosomes and identifies an RNA-based cancer-specific strategy to overcome intrinsic resistance to ICB.
Developing hippocampal spheroids model ictogenesis and epileptogenesis
Authors: Ephraim John Wesley , Caron Davide , Canal-Alonso Angel , Corchado Juan Manuel , Palazzolo Gemma , Panuccio Gabriella 
Published: January 2023

AbstractThree-dimensional (3D) neural cell cultures inherently lend themselves to high-throughput network electrophysiology studies addressing brain function in health and disease in a more realistic architectural complexity than two-dimensional neural networks. Epilepsy is the emblem of brain network disorders, as it reflects aberrant circuit reorganization and hyper-synchronization, resulting in sudden and uncontrolled electrical discharges (seizures). Modeling the features of epilepsy has so far relied on pharmacological, ionic or genetic manipulation of cells, ex-vivo brain tissue or intact animals, failing to recapitulate most of the epilepsies, which are triggered by unknown causes. Here, we report the spontaneous emergence of epileptiform patterns in spheroids of rodent primary hippocampal cells cultured in physiological condition, i.e., in the absence of a known initiating insult, detected by microelectrode array electrophysiology. Three distinct electrical phenotypes, i.e. interictal (between seizures), ictal (seizure) or mixed, arise from DIV10 to DIV35. In particular, the tonic-clonic ictal discharges become the most prominent at DIV28-35. These patterns exhibit electrographic and spectral features that strikingly resemble those observed in the hippocampus of in vitro and in vivo rodent epilepsy models, as well as of drug-resistant epileptic humans. Remarkably, not all spheroids exhibit full-blown ictal activity, bringing parallelism with the yet unanswered question of why a brain becomes epileptic and a seizure is generated. This evidence warrants caution against hippocampal cell-based therapies for regenerative purposes, as they may initiate epileptogenesis; at the same time, hippocampal spheroids lend themselves as reductionist model supporting high-throughput pre-clinical research on epileptic syndromes involving the hippocampus.
Genomes of the human filarial parasitesMansonella perstansandMansonella ozzardi
Authors: Sinha Amit , Li Zhiru , Poole Catherine B. , Morgan Richard D. , Ettwiller Laurence , Lima Nathália F. , Ferreira Marcelo U. , Fombad Fanny F. , Wanji Samuel , Carlow Clotilde K. S. 
Published: January 2023

AbstractThe filarial parasitesMansonella ozzardiandMansonella perstans, causative agents of mansonellosis, infect hundreds of millions of people worldwide, yet remain among the most understudied of the human filarial pathogens.M. ozzardiis highly prevalent in Latin American countries and Caribbean Islands, whileM. perstansis predominantly found in sub-Saharan Africa as well as in a few areas in South America. In addition to the differences in their geographical distribution, the two parasites are transmitted by different insect vectors, as well as exhibit differences in their responses to commonly used anthelminthic drugs. The lack of genome information has hindered investigations into the biology and evolution ofMansonellaparasites and understanding the molecular basis of the clinical differences between species. In the current study, high quality genomes of two independent clinical isolates ofM. perstansfrom Cameroon and twoM. ozzardiisolates one from Brazil and one from Venezuela are reported. The genomes are approximately 76 Mb in size, encode about 10,000 genes each, and are largely complete based on BUSCO scores of about 90%, similar to other completed filarial genomes. These sequences represent the first genomes fromMansonellaparasites and enabled a comparative genomic analysis of the similarities and differences betweenMansonellaand other filarial parasites. Horizontal DNA transfers (HDT) from mitochondria (nuMTs) as well as transfers from genomes of endosymbioticWolbachiabacteria (nuWTs) to the host nuclear genome were identified and analyzed. Sequence comparisons and phylogenetic analysis of known targets of anti-filarial drugs diethylcarbamazine (DEC), ivermectin and mebendazole revealed that all known target genes were present in both species, except for the DEC target encoded bygon-2gene, which is fragmented in genome assemblies from bothM. ozzardiisolates. These new reference genome sequences will provide a valuable resource for further studies on biology, symbiosis, evolution and drug discovery.
Contrast Sensitivity Function in Deep Networks
Authors: Akbarinia Arash , Morgenstern Yaniv , Gegenfurtner Karl R. 
Published: January 2023

AbstractThe contrast sensitivity function (CSF) is a fundamental signature of the visual system that has been measured extensively in several species. It is defined by the visibility threshold for sinusoidal gratings at all spatial fre-quencies. Here, we investigated the CSF in deep neural networks using the same 2AFC contrast detection paradigm as in human psychophysics. We examined 240 networks pretrained on several tasks. To obtain their corre-sponding CSFs, we trained a linear classifier on top of the extracted features from frozen pretrained networks. The linear classifier is exclusively trained on a contrast discrimination task with natural images. It has to find which of the two input images has higher contrast. The network’s CSF is measured by detecting which one of two images contains a sinusoidal grating of varying orientation and spatial frequency. Our results demonstrate char-acteristics of the human CSF are manifested in deep networks both in the luminance channel (a band-limited inverted U-shaped function) and in the chromatic channels (two low-pass functions of similar properties). The exact shape of the networks’ CSF appears to be task-dependent. The human CSF is better captured by networks trained on low-level visual tasks such as image-denoising or autoencoding. However, human-like CSF also emerges in mid- and high-level tasks such as edge detection and object recognition. Our analysis shows that human-like CSF appears in all architectures but at different depths of processing, some at early layers, while others in intermediate and final layers. Overall, these results suggest that (i) deep networks model the human CSF faithfully, making them suitable candidates for applications of image quality and compression, (ii) efficient/purposeful processing of the natural world drives the CSF shape, and (iii) visual representation from all levels of visual hierarchy contribute to the tuning curve of the CSF, in turn implying a function which we intuitively think of as modulated by low-level visual features may arise as a consequence of pooling from a larger set of neurons at all levels of the visual system.
Myristoylated Neuronal Calcium Sensor-1 captures the ciliary vesicle at distal appendages
Authors: Kanie Tomoharu , Ng Roy , Abbott Keene L. , Pongs Olaf , Jackson Peter K. 
Published: January 2023

SummaryThe primary cilium is a microtubule-based organelle that cycles through assembly and disassembly. In many cell types, formation of the cilium is initiated by recruitment of ciliary vesicles to the distal appendage of the mother centriole. However, the distal appendage mechanism that directly captures ciliary vesicles is yet to be identified. In an accompanying paper, we show that the distal appendage protein, CEP89, is important for thef ciliary vesicle recruitment, but not for other steps of cilium formation (Tomoharu Kanie, Love, Fisher, Gustavsson, & Jackson, 2023). The lack of a membrane binding motif in CEP89 suggests that it may indirectly recruit ciliary vesicles via another binding partner. Here, we identify Neuronal Calcium Sensor-1 (NCS1) as a stoichiometric interactor of CEP89. NCS1 localizes to the position between CEP89 and a ciliary vesicle marker, RAB34, at the distal appendage. This localization was completely abolished in CEP89 knockouts, suggesting that CEP89 recruits NCS1 to the distal appendage. Similarly to CEP89 knockouts, ciliary vesicle recruitment as well as subsequent cilium formation was perturbed in NCS1 knockout cells. The ability of NCS1 to recruit the ciliary vesicle is dependent on its myristoylation motif and NCS1 knockout cells expressing myristoylation defective mutant failed to rescue the vesicle recruitment defect despite localizing proper localization to the centriole. In sum, our analysis reveals the first known mechanism for how the distal appendage recruits the ciliary vesicles.
NMDA Receptors Control Activity Hierarchy in Neural Network: Loss of Control in Hierarchy Leads to Learning Impairments, Dissociation, and Psychosis
Authors: Zhou Yuxin , Wang Jenn Lingshu , Qiu Liyan , Torpey Jordan , Wixson Jemma Glenn , Lyon Mark , Chen Xuanmao 
Published: January 2023

AbstractWhile it is known that associative memory is preferentially encoded by memory-eligible “primed” neurons,in vivoneural activity hierarchy has not been quantified and little is known about how such a hierarchy is established. Leveragingin vivocalcium imaging of hippocampal neurons on freely behaving mice, we developed the first method to quantify real-time neural activity hierarchy in the CA1 region. Neurons at the top of activity hierarchy are identified as primed neurons. In cilia knockout mice that exhibit severe learning deficits, the percentage of primed neurons is drastically reduced. We developed a simplified neural network model that incorporates simulations of linear and non-linear weighted components, modeling the synaptic ionic conductance of AMPA and NMDA receptors, respectively. We found that moderate non-linear to linear conductance ratios naturally leads a small fraction of neurons to be primed in the simulated neural network. Removal of the non-linear component eliminates the existing activity hierarchy and reinstate it to the network stochastically primes a new pool of neurons. Blockade of NMDA receptors by ketamine not only decreases general neuronal activity causing learning impairments, but also disrupts neural activity hierarchy. Additionally, ketamine-induced super-synchronized slow oscillation during anesthesia can be simulated if the non-linear NMDAR component is removed to flatten activity hierarchy. Together, this study develops a unique method to measure neural activity hierarchy and identifies NMDA receptors as a key factor that controls the hierarchy. It presents the first evidence suggesting that hierarchy disruption by NMDAR blockade causes dissociation and psychosis.
Convergent behavior of extended stalk regions from staphylococcal surface proteins with widely divergent sequence patterns
Authors: Yarawsky Alexander E. , Ori Andrea L. , English Lance R. , Whitten Steven T. , Herr Andrew B. 
Published: January 2023

AbstractStaphylococcus epidermidisandS. aureusare highly problematic bacteria in hospital settings. This stems, at least in part, from strong abilities to form biofilms on abiotic or biotic surfaces. Biofilms are well-organized multicellular aggregates of bacteria, which, when formed on indwelling medical devices, lead to infections that are difficult to treat. Cell wall-anchored (CWA) proteins are known to be important players in biofilm formation and infection. Many of these proteins have putative stalk-like regions or regions of low complexity near the cell wall-anchoring motif. Recent work demonstrated the strong propensity of the stalk region of theS. epidermidisaccumulation-associated protein (Aap) to remain highly extended under solution conditions that typically induce compaction or other significant conformational changes. This behavior is consistent with the expected function of a stalk-like region that is covalently attached to the cell wall peptidoglycan and projects the adhesive domains of Aap away from the cell surface. In this study, we evaluate whether the ability to resist compaction is a common theme among stalk regions from various staphylococcal CWA proteins. Circular dichroism spectroscopy was used to examine secondary structure changes as a function of temperature and cosolvents along with sedimentation velocity analytical ultracentrifugation and SAXS to characterize structural characteristics in solution. All stalk regions tested are intrinsically disordered, lacking secondary structure beyond random coil and polyproline type II helix, and they all sample highly extended conformations. Remarkably, the Ser-Asp dipeptide repeat region of SdrC exhibited nearly identical behavior in solution when compared to the Aap Pro/Gly-rich region, despite highly divergent sequence patterns, indicating conservation of function by various distinct staphylococcal CWA protein stalk regions.
Anaerobe isolation from denitrifying benzene-degrading enrichment culture and their capacity to mineralize benzene
Authors: Eziuzor Samuel C , Vogt Carsten 
Published: January 2023

AbstractOnly a few benzene-mineralizing anaerobes have been isolated to date. In an attempt using classical isolation techniques to isolate benzene-mineralizing pure cultures from a benzene-mineralizing nitrate-reducing microbial community, two putative isolates were gained under nitrate-reducing conditions spiked separately with acetate and benzene as sole sources of carbon and energy with media containing ammonium or without ammonium. Both putative isolates; Bz4 (with ammonium) and Bz7 (without ammonium) - mineralized13C-labelled acetate under anoxic conditions at 3.3 and 2.7 μM day-1, respectively, revealed by analysis of evolved13CO2. However, only Bz4 mineralized [13C6]-labelled benzene (0.298 μM benzene mineralized day-1) generated up to 960.2 ± 0.3 ‰ δ13C-CO2during 184 days while producing only slight amounts of nitrite (4.60 ± 0.004 μM); no benzene was mineralized by Bz7 during 184 d, and no nitrite was detected. The 16S rRNA gene amplicon sequencing of the acetate-grown bacteria revealed consortia enriched inNocardioides(8.9%),Pseudomonas(18.2%),Rhizobiaceae(21.0%),Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium(51.4%) for Bz4 and Simplicispira(96.7%) for Bz7. The gained Bz4 consortium that mineralized benzene under anoxic condition can be further purified and explored for their metabolic potentials.
Habitat amount, temperature and biotic interactions drive community structure, life-history traits, and performance traits of cavity-nesting bees and wasps and their natural enemies in cities
Authors: Casanelles-Abella Joan , Pellissier Loïc , Aleixo Cristiana , Orti Marta Alós , Chiron François , Deguines Nicolas , Laanisto Lauri , Myczko Łukasz , Niinemets Ülo , Pinho Pedro , Samson Roeland , Tryjanowski Piotr , Villarroya-Villalba Lucía , Moretti Marco 
Published: January 2023

AbstractUrban ecosystems are associated with socio-ecological conditions that can filter and promote taxa. However, the strength of the effect of ecological filtering on biodiversity could vary among biotic and abiotic factors. Here, we investigate the effects of habitat amount, temperature, and host-enemy biotic interactions in shaping communities of cavity-nesting bees and wasps (CNBW) and their natural enemies.We installed trap-nests in 80 sites distributed along urban intensity gradients in 5 European cities (Antwerp, Paris, Poznan, Tartu and Zurich). We quantified the species richness and abundance of CNBW hosts and their natural enemies, as well as two performance traits (survival and parasitism) and two life-history traits (sex ratio and number of offspring per nest for the hosts). We analysed the importance of the abiotic and biotic variables using generalized linear models and multi-model inference.We found that habitat amount and temperature were the main drivers of CNBW host responses, with larger habitat amounts resulting in higher species richness and abundance, and a larger total number of brood cells per nest for both bees and wasps, as well as a larger probability of survival for bees. Conversely, higher local temperatures decreased species richness, abundance, survival rate, number of brood cells per nest, and proportion of females in CNBW hosts.Biotic interactions with natural enemies shaped wasp species richness, with higher levels of parasitism resulting in more wasp species. Similarly, our results showed direct density-dependence between CNBW hosts and their natural enemies.Overall, our study highlights the importance of habitat amount and temperature in shaping urban food webs, through direct effects on hosts responses and the subsequent consequences for their natural enemies. As cities prepare to tackle the future consequences of global change, strategies that make it possible to maintain available habitat and mitigate urban overheating emerge as a key urban adaptation for biodiversity conservation.
Marine heatwaves threaten cryptic coral diversity and erode associations amongst coevolving partners
Authors: Starko Samuel , Fifer James , Claar Danielle C. , Davies Sarah W. , Cunning Ross , Baker Andrew C. , Baum Julia K. 
Published: January 2023

AbstractClimate change-amplified heatwaves are known to drive extensive mortality in marine foundation species. However, a paucity of longitudinal genomic datasets has impeded understanding of how these rapid selection events alter species’ genetic structure. Impacts of these events may be exacerbated in species with obligate symbioses, where the genetics of multiple co-evolving species may be affected. Here, we tracked the symbiotic associations and fate of reef-building corals for six years through a prolonged heatwave. Coral genetics strongly predicted survival of the common coralPoritesthrough the event, with strong differential survival (15 to 64%) apparent across morphologically identical -but genetically distinct- lineages. The event also disrupted strong associations between coral lineages and their symbiotic partners, homogenizing symbiotic assemblages across lineages and reducing the specificity of coral-algal symbioses. These results highlight that marine heatwaves threaten cryptic genetic diversity of foundation species and have the potential to decouple tight relationships between co-evolving host-symbiont pairs.
Immune response modulation byPseudomonas aeruginosapersister cells
Authors: Hastings Cody James , Himmler Grace Elizabeth , Patel Arpeet , Marques Cláudia Nogueira Hora 
Published: January 2023

AbstractBacterial persister cells – a metabolically dormant subpopulation tolerant to antimicrobials – contribute to chronic infections and are thought to evade host immunity. In this work, we studied the ability ofPseudomonas aeruginosapersister cells to withstand host innate immunity. We found that persister cells resist MAC-mediated killing by the complement system despite being bound by complement protein C3b at levels similar to regular vegetative cells, in part due to reduced bound C5b - and are engulfed at a lower rate (10-100 fold), even following opsonization. Once engulfed, persister cells resist killing and, contrary to regular vegetative cells which induce a M1 favored (CD80+/CD86+/CD206-, high levels of CXCL-8, IL-6, and TNF-α) macrophage polarization, they initially induce a M2 favored macrophage polarization (CD80+/CD86+/CD206+, high levels of IL-10, and intermediate levels of CXCL-8, IL-6, and TNF-α), which is skewed towards M1 favored polarization (high levels of CXCL-8 and IL-6, lower levels of IL-10) by 24 hours of infection, once persister cells awaken. Overall, our findings further establish the ability of persister cells to evade the innate host response and to contribute chronic infections.
A converged ubiquitin-proteasome pathway for the degradation of TOC and TOM tail-anchored receptors
Authors: Yang Meijing , Chen Shuai , Lim Shey-Li , Yang Lang , Zhong Jia Yi , Chan Koon Chuen , Zhao Zhizhu , Wong Kam-Bo , Wang Junqi , Lim Boon Leong 
Published: January 2023

ABSTRACTIn plants, thousands of nucleus-encoded proteins translated in the cytosol are sorted to chloroplasts and mitochondria by binding to specific receptors of the TOC (translocon at the outer membranes of chloroplasts) and the TOM (translocon at the outer membranes of mitochondria) complexes for import into those organelles. The degradation pathways for these receptors are unclear. Here, we discovered a converged ubiquitin-proteasome pathway for the degradation ofArabidopsis thalianaTOC and TOM tail-anchored receptors. The receptors are ubiquitinated by E3 ligase(s) and pulled from the outer membranes by the AAA+ATPase CDC48, after which a previously characterized cytosolic protein, TTOP, binds to the exposed transmembrane domains (TMDs) at the C termini of the receptors and CDC48, and delivers these complexes to the 26S proteasome.
If it’s real, could it be an eel?
Authors: Foxon Floe 
Published: January 2023

AbstractPrevious studies have estimated the size, mass, and population of hypothetical unknown animals in a large, oligotrophic freshwater loch in Scotland based on biomass and other observational considerations. The ‘eel hypothesis’ proposes that the anthrozoological phenomenon at Loch Ness can be explained in part by observations of large specimens of European eel (Anguilla anguilla), as these animals are most compatible with morphological, behavioural, and environmental considerations. The present study expands upon the ‘eel hypothesis’ and related literature by estimating the probability of observing eels at least as large as have been proposed, using catch data from Loch Ness and other freshwater bodies in Europe. Skew normal and generalized extreme value distributions were fitted to eel body length distributions in order to estimate cumulative distribution functions from which probabilities were obtained. The chances of finding a large eel in Loch Ness are around 1 in 50, 000 for a 1-meter specimen, which is reasonable given the loch’s fish stock and suggests some sightings of smaller ‘unknown’ animals may be accounted for by large eels. However, the probability of finding a specimen upwards of 6 meters is essentially zero, therefore eels probably do not account for ‘sightings’ of larger animals. The existence of exceedingly large eels in the loch is not likely based on purely statistical considerations.