bluuebunny/crossref_metadata_2025_split huggingface dataset:
Voronota-LT: efficient, flexible and solvent-aware tessellation-based analysis of atomic interactions
Authors: Olechnovič Kliment , Grudinin Sergei 
Published: February 2024

AbstractMotivationIn the fields of structural biology and bioinformatics, understanding molecular interactions is paramount. However, existing advanced geometric methods for describing interatomic contacts considering full structural context have typically demanded substantial computational resources, hindering their practical application. Given the ever-growing volume of structural data, there is an urgent need for more efficient tools for interaction analysis.ResultsWe present Voronota-LT, a new efficient method tailored for computing Voronoi tessellation-based atom-atom contacts within the solvent-accessible surface of molecular structures. Voronota-LT constructs every interatomic contact surface directly, without pre-computing the global Voronoi diagram or Delaunay triangulation. This approach results in a method that is not only fast, but also parallelizable and capable of selectively targeting specific interface areas within molecular complexes. While offering high execution speed, Voronota-LT provides a comprehensive description of every interatomic interaction, taking full account of the relevant structural context.Availability and ImplementationVoronota-LT software is freely available as both a standalone application and a C++ header-only library athttps://kliment-olechnovic.github.io/voronota/expansion_lt/.
Coordinated active repression operates via transcription factor cooperativity and multiple inactive promoter states in a developing organism
Authors: Pimmett Virginia , Douaihy Maria , Maillard Louise , Trullo Antonio , Garcia Idieder Pablo , Costes Melissa , Dufourt Jeremy , Lenden-Hasse Helene , Radulescu Ovidiu , Lagha Mounia 
Published: February 2024

AbstractRefining transcriptional levels via active repression in an euchromatic context represents a critical regulatory process. While the molecular players of active repression are well described, their dynamics remain obscure. Here, we usedsnailexpression dynamics as a paradigm to uncover how repression, mediated by the Snail (Sna) repressor, can be imposed within a developing tissue. Combining live imaging and mathematical modeling, we show that Sna-mediated repression is cooperative and that cooperativity is primarily mediated by the distal enhancer. Repression shifts transcription bursting dynamics from a two-state ON/OFF regime to a three-state repressed regime with two temporally distinct OFF states. Mutating Sna binding sites suggests that repression introduces the long-lasting inactive state, which is stabilized by cooperativity. Our approach offers quantitative insights into the dynamics of repression and how transcription factor cooperativity coordinates cell fate decisions within a tissue.
PlasmodiumNEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation
Authors: Zeeshan Mohammad , Rashpa Ravish , Ferguson David J. , Mckeown George , Nugmanova Raushan , Subudhi Amit K. , Beyeler Raphael , Pashley Sarah L. , Markus Robert , Brady Declan , Roques Magali , Bottrill Andrew R. , Fry Andrew M. , Pain Arnab , Vaughan Sue , Holder Anthony A. , Tromer Eelco C. , Brochet Mathieu , Tewari Rita 
Published: February 2024

AbstractMitosis is an important process in the cell cycle required for cells to divide. Never in mitosis (NIMA)-like kinases (NEKs) are regulators of mitotic functions in diverse organisms.Plasmodium spp, the causative agent of malaria is a divergent unicellular haploid eukaryote with some unusual features in terms of its mitotic and nuclear division cycle that presumably facilitate proliferation in varied environments. For example, during the sexual stage of male gametogenesis that occurs within the mosquito host, an atypical rapid closed endomitosis is observed. Three rounds of genome replication from 1N to 8N and successive cycles of multiple spindle formation and chromosome segregation occur within eight minutes followed by karyokinesis to generate haploid gametes.Our previousPlasmodium bergheikinome screen identified fourNekgenes, of which two, NEK2 and NEK4, are required for meiosis. NEK1 is likely to be essential for mitosis in asexual blood stage schizogony in the vertebrate host, but its function during male gametogenesis is unknown. Here, we study NEK1 location and function, using live cell imaging, ultrastructure expansion microscopy (U-ExM) and electron microscopy, together with conditional gene knockdown and proteomic approaches. We report spatiotemporal NEK1 location in real-time, coordinated with microtubule organising centre (MTOC) dynamics during the unusual mitoses at various stages of thePlasmodium spp.life cycle. Knockdown studies reveal NEK1 to be an essential component of the MTOC in male cell differentiation, associated with rapid mitosis, spindle formation and kinetochore attachment. These data suggest thatPlasmodium bergheiNEK1 kinase is an important component of MTOC organisation and essential regulator of chromosome segregation during male gamete formation.
Circadian rhythmicity and photobiological mechanisms of light sensitivity and discomfort glare in humans
Authors: Daguet I , Raverot V , Gronfier C 
Published: February 2024

AbstractDiscomfort glare is a common visual sensation, which is generally reported when being exposed to a brighter lit environment. In certain clinical conditions, this sensation is abnormally amplified, and is commonly named photophobia. Despite the frequent appearance of this sensation in everyday life or in pathological conditions, the underlying mechanisms remain poorly understood. We show here, in highly controlled laboratory constant routine conditions, that light-induced discomfort glare is rhythmic over the 24-hour day. We reveal a strong circadian drive, with a sinusoidal rhythmicity, with maximal discomfort glare in the middle of the night and minimal in the afternoon. We also find a modest sleep-related homeostatic drive of visual discomfort, with a linear increase in discomfort glare over 34 hours of prolonged wakefulness. Our study reveals that discomfort glare is primarily driven by the ipRGC pathway, and that mid and/or long wavelengths cones are involved as well. The 6.5-hour phase lag between the rhythms of photoreceptors’ sensitivity, assessed through pupillary light reflex, and of glare discomfort, suggests two independent underlying mechanisms. In conclusion, our findings highlight the need to take time-of-day and biological rhythmicity into account in the evaluation of light-induced discomfort glare. Apprehending these mechanisms may help understand photophobia in clinical populations, such as in migraine patients, and should be taken into account to optimize light quality at home and at the workplace, both for day and night work.
MEA-NAP compares microscale functional connectivity, topology, and network dynamics in organoid or monolayer neuronal cultures
Authors: Sit Timothy PH , Feord Rachael C , Dunn Alexander WE , Chabros Jeremi , Oluigbo David , Smith Hugo H , Burn Lance , Chang Elise , Boschi Alessio , Yuan Yin , Gibbons George M , Khayat-Khoei Mahsa , De Angelis Francesco , Hemberg Erik , Hemberg Martin , Lancaster Madeline A , Lakatos Andras , Eglen Stephen J , Paulsen Ole , Mierau Susanna B 
Published: February 2024

SummaryMicroelectrode array (MEA) recordings are commonly used to compare firing and burst rates in neuronal cultures. MEA recordings can also reveal microscale functional connectivity, topology, and network dynamics—patterns seen in brain networks across spatial scales. Network topology is frequently characterized in neuroimaging with graph theoretical metrics. However, few computational tools exist for analyzing microscale functional brain networks from MEA recordings. Here, we present a MATLAB MEA network analysis pipeline (MEA-NAP) for raw voltage time-series acquired from single- or multi-well MEAs. Applications to 3D human cerebral organoids or 2D human-derived or murine cultures reveal differences in network development, including topology, node cartography, and dimensionality. MEA-NAP incorporates multi-unit template-based spike detection, probabilistic thresholding for determining significant functional connections, and normalization techniques for comparing networks. MEA-NAP can identify network-level effects of pharmacologic perturbation and/or disease-causing mutations and, thus, can provide a translational platform for revealing mechanistic insights and screening new therapeutic approaches.
Preservation of memory B cell homeostasis in an individual producing broadly neutralising antibodies against HIV-1
Authors: Griffith Sarah , Muir Luke , Suchanek Ondrej , Hope Joshua , Pade Corinna , Gibbons Joseph M , Tuong Zewen Kelvin , Fung Audrey , Touizer Emma , Rees-Spear Chloe , Nans Andrea , Roustan Chloe , Alguel Yilmaz , Fink Douglas , Orkin Chloe , Deayton Jane , Anderson Jane , Gupta Ravindra K , Doores Katie J , Cherepanov Peter , McKnight Áine , Clatworthy Menna , McCoy Laura E 
Published: February 2024

AbstractImmunological determinants favouring emergence of broadly neutralising antibodies are crucial to the development of HIV-1 vaccination strategies. Here, we combined RNAseq and B cell cloning approaches to isolate a broadly neutralising antibody (bnAb) ELC07 from an individual living with untreated HIV-1. Using single particle cryogenic electron microscopy (cryo-EM), we show that the antibody recognises a conformational epitope at the gp120-gp41 interface. ELC07 binds the closed state of the viral glycoprotein causing considerable perturbations to the gp41 trimer core structure. Phenotypic analysis of memory B cell subsets from the ELC07 bnAb donor revealed a lack of expected HIV-1-associated dysfunction, specifically no increase in CD21-/CD27-cells was observed whilst the resting memory (CD21+/CD27+) population appeared preserved despite uncontrolled HIV-1 viraemia. Moreover, single cell transcriptomes of memory B cells from this bnAb donor showed a resting memory phenotype irrespective of the epitope they targeted or their ability to neutralise diverse strains of HIV-1. Strikingly, single memory B cells from the ELC07 bnAb donor were transcriptionally similar to memory B cells from HIV-negative individuals. Our results demonstrate that potent bnAbs can arise without the HIV-1-induced dysregulation of the memory B cell compartment and suggest that sufficient levels of antigenic stimulation with a strategically designed immunogen could be effective in HIV-negative vaccine recipients.
Kappa Opioid Receptors Negatively Regulate Real Time Spontaneous Dopamine Signals by Reducing Release and Increasing Uptake
Authors: Wallace Conner W , Holleran Katherine M , Slinkard Clare Y , Centanni Samuel W , Jones Sara R 
Published: February 2024

AbstractThe role of the dynorphin/kappa opioid receptor (KOR) system in dopamine (DA) regulation has been extensively investigated. KOR activation reduces extracellular DA concentrations and increases DA transporter (DAT) activity and trafficking to the membrane. To explore KOR influences on real-time DA fluctuations, we used the photosensor dLight1.2 with fiber photometry in the nucleus accumbens (NAc) core of freely moving male and female C57BL/6 mice. First, we established that the rise and fall of spontaneous DA signals were due to DA release and reuptake, respectively. Then mice were systemically administered the KOR agonist U50,488H (U50), with or without pretreatment with the KOR antagonist aticaprant (ATIC). U50 reduced both the amplitude and width of spontaneous signals in males, but only reduced width in females. Further, the slope of the correlation between amplitude and width was increased in both sexes, suggesting that DA uptake rates were increased. U50 also reduced the frequency of signals in both males and females. All effects of KOR activation were stronger in males. Overall, KORs exerted significant inhibitory control over spontaneous DA signaling, acting through at least three mechanisms - inhibiting DA release, promoting DAT-mediated uptake, and reducing the frequency of signals.
WildPose: A Long-Range 3D Wildlife Motion Capture System
Authors: Muramatsu Naoya , Shin Sangyun , Deng Qianyi , Markham Andrew , Patel Amir 
Published: February 2024

ABSTRACTUnderstanding and monitoring wildlife behavior is crucial in ecology and biomechanics, yet challenging due to the limitations of current methods. To address this issue, we introduce WildPose, a novel long-range motion capture system specifically tailored for free-ranging wildlife observation. This system combines an electronically controllable zoom-lens camera with a LiDAR to capture both 2D videos and 3D point cloud data, thereby allowing researchers to observe high-fidelity animal morphometrics, behavior and interactions in a completely remote manner. Field trials conducted in Kgalagadi Transfrontier Park have successfully demonstrated WildPose’s ability to quantify morphological features of different species, accurately track the 3D movements of a springbok herd over time, and observe the respiratory patterns of a distant lion. By facilitating non-intrusive, long-range 3D data collection, WildPose marks a significant complementary technique in ecological and biomechanical studies, offering new possibilities for conservation efforts and animal welfare, and enriching the prospects for interdisciplinary research.
Translational activation by a synthetic PPR protein elucidates control ofpsbAtranslation in Arabidopsis chloroplasts
Authors: Rojas Margarita , Chotewutmontri Prakitchai , Barkan Alice 
Published: February 2024

AbstractTranslation initiation onpsbAmRNA in plant chloroplasts scales with light intensity, providing its gene product, D1, to replace photodamaged D1 in Photosystem II. ThepsbAtranslational activator HCF173 has been hypothesized to mediate this regulation. HCF173 belongs to the short-chain dehydrogenase/reductase superfamily, associates with thepsbA5’-untranslated region (5’-UTR), and has been hypothesized to enhance translation by binding an RNA segment that would otherwise pair with and mask the ribosome binding region. To test these hypotheses, we examined whether a synthetic pentatricopeptide repeat (sPPR) protein can substitute for HCF173 when bound to the HCF173 binding site. We show that an sPPR designed to bind HCF173’s footprint in thepsbA5’-UTR bound the intended sitein vivoand partially substituted for HCF173 to activatepsbAtranslation. However, sPPR-activated translation did not respond to light. These results imply that HCF173 activates translation, at least in part, by sequestering the RNA it binds to maintain an accessible ribosome binding region, and that HCF173 is also required to regulatepsbAtranslation in response to light. Translational activation can be added to the functions that can be programmed with sPPR proteins for synthetic biology applications in chloroplasts.One sentence summaryA synthetic PPR protein substitutes for HCF173, a non-PPR translational activator in chloroplasts, elucidating HCF173 functions and demonstrating the ability of synthetic PPRs to activate translation.
Fine-scale tracking reveals visual field use for predator detection and escape in collective foraging of pigeon flocks
Authors: Delacoux Mathilde , Kano Fumihiro 
Published: February 2024

AbstractDuring collective vigilance, it is commonly assumed that individual animals compromise their feeding time to be vigilant against predators, benefiting the entire group. One notable issue with this assumption concerns the unclear nature of predator “detection”, particularly in terms of vision. It remains uncertain how a vigilant individual utilizes its high-acuity vision (such as the fovea) to detect a predator cue and subsequently guide individual and collective escape responses. Using fine-scale motion capture technologies, we tracked the head and body orientations of pigeons (hence reconstructed their visual fields and foveal projections) foraging in a flock during simulated predator attacks. Pigeons used their fovea to inspect predator cues. Earlier foveation on a predator cue was linked to preceding behaviors related to vigilance and feeding, such as head-up or down positions, head-scanning, and food-pecking. Moreover, earlier foveation predicted earlier evasion flights at both the individual and collective levels. However, we also found that relatively long delay between their foveation and escape responses in individuals obscured the relationship between these two responses. While our results largely support the existing assumptions about vigilance, they also underscore the importance of considering vision and addressing the disparity between detection and escape responses in future research.
Second Boost of Omicron SARS-CoV-2 S1 Subunit Vaccine Induced Broad Humoral Immune Responses in Elderly Mice
Authors: Kim Eun , Khan Muhammad S. , Ferrari Alessandro , Huang Shaohua , Kenniston Thomas W. , Cassaniti Irene , Baldanti Fausto , Gambotto Andrea 
Published: February 2024

AbstractCurrently approved COVID-19 vaccines prevent symptomatic infection, hospitalization, and death from the disease. However, repeated homologous boosters, while considered a solution for severe forms of the disease caused by new SARS-CoV-2 variants in elderly individuals and immunocompromised patients, cannot provide complete protection against breakthrough infections. This highlights the need for alternative platforms for booster vaccines. In our previous study, we assessed the boost effect of the SARS-CoV-2 Beta S1 recombinant protein subunit vaccine (rS1Beta) in aged mice primed with an adenovirus-based vaccine expressing SARS-CoV-2-S1 (Ad5.S1) via subcutaneous injection or intranasal delivery, which induced robust humoral immune responses (1). In this follow-up study, we demonstrated that a second booster dose of a non-adjuvanted recombinant Omicron (BA.1) S1 subunit vaccine with Toll-like receptor 4 (TLR4) agonist RS09 (rS1RS09OM) was effective in stimulating strong S1-specific immune responses and inducing significantly high neutralizing antibodies against the Wuhan, Delta, and Omicron variants in 100-week-old mice. Importantly, the second booster dose elicits cross-reactive antibody responses, resulting in ACE2 binding inhibition against the spike protein of SARS-CoV-2 variants, including Omicron (BA.1) and its subvariants. Interestingly, the levels of IgG and neutralizing antibodies correlated with the level of ACE2 inhibition in the booster serum samples, although Omicron S1-specific IgG level showed a weaker correlation compared to Wuhan S1-specific IgG level. Furthermore, we compared the immunogenic properties of the rS1 subunit vaccine in young, middle-aged, and elderly mice, resulting in reduced immunogenicity with age, especially an impaired Th1-biased immune response in aged mice. Our findings demonstrate that the new variant of concern (VOC) rS1 subunit vaccine as a second booster has the potential to offer cross-neutralization against a broad range of variants and to improve vaccine effectiveness against newly emerging breakthrough SARS-CoV-2 variants in elderly individuals who were previously primed with the authorized vaccines.
PI3K/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis
Authors: Liu Gang , Hou Yunxuan , Jin Xin , Zhang Yixue , Sun Chaoyue , Huang Chengquan , Ren Yujie , Gao Jianmin , Wang Xiuli , Jiang Xiumei 
Published: February 2024

AbstractErythropoiesis and megakaryopoiesis are stringently regulated by signaling pathways. However, the precise molecular mechanisms through which signaling pathways regulate key transcription factors controlling erythropoiesis and megakaryopoiesis remain partially understood. Herein, we identified heat shock cognate B (HSCB), which is well known for its iron-sulfur cluster delivery function, as an indispensable protein for friend of GATA 1 (FOG1) nuclear translocation during erythropoiesis of K562 human erythroleukemia cells and cord-blood-derived human CD34+CD90+ hematopoietic stem cells (HSCs), as well as during megakaryopoiesis of the CD34+CD90+ HSCs. Mechanistically, HSCB could be phosphorylated by phosphoinositol-3-kinase (PI3K) to bind with and mediate the proteasomal degradation of transforming acidic coiled-coil containing protein 3 (TACC3), which otherwise detained FOG1 in the cytoplasm, thereby facilitating FOG1 nuclear translocation. Given that PI3K is activated during both erythropoiesis and megakaryopoiesis, and that FOG1 is a key transcription factor for these processes, our findings elucidate an important, previously unrecognized iron-sulfur cluster delivery independent function of HSCB in erythropoiesis and megakaryopoiesis.
A comprehensive examination of Chelicerate genomes reveals no evidence for a whole genome duplication among spiders and scorpions
Authors: Thomas Gregg W.C. , McKibben Michael T.W. , Hahn Matthew W. , Barker Michael S. 
Published: February 2024

AbstractWhole genome duplications (WGDs) can be a key event in evolution, playing a role in both adaptation and speciation. While WGDs are common throughout the history of plants, only a few examples have been proposed in metazoans. Among these, recent proposals of WGD events in Chelicerates, the group of Arthropods that includes horseshoe crabs, ticks, scorpions, and spiders, include several rounds in the history of horseshoe crabs, with an additional WGD proposed in the ancestor of spiders and scorpions. However, many of these inferences are based on evidence from only a small portion of the genome (in particular, theHoxgene cluster); therefore, genome-wide inferences with broader species sampling may give a clearer picture of WGDs in this clade. Here, we investigate signals of WGD in Chelicerates using whole genomes from 17 species. We employ multiple methods to look for these signals, including gene tree analysis of thousands of gene families, comparisons of synteny, and signals of divergence among within-species paralogs. We test several scenarios of WGD in Chelicerates using multiple species trees as a backbone for all hypotheses. While we do find support for at least one WGD in the ancestral horseshoe crab lineage, we find no evidence for a WGD in the history of spiders and scorpions using any genome-scale method. This study not only sheds light on genome evolution and phylogenetics within Chelicerates, but also demonstrates how a combination of comparative methods can be used to investigate signals of ancient WGDs.