bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macaque amygdala, claustrum and pulvinar support the cross-modal association of social audio-visual stimuli based on meaning
Authors: Froesel Mathilda , Gacoin Maëva , Clavagnier Simon , Hauser Marc , Goudard Quentin , Ben Hamed Suliann 
Published: September 2022

AbstractSocial communication draws on several cognitive functions such as perception, emotion recognition and attention. In a previous study, we demonstrated that macaques associate audiovisual information when processing their species-specific communicative signals. Specifically, cortical activation is inhibited when there is a mismatch between vocalisations and social visual information whereas activation is enhanced in the lateral sulcus, superior temporal sulcus as well as a larger network composed of early visual and prefrontal areas when vocalisations and social visual information match. Here, we use a similar task and functional magnetic resonance imaging to assess the role of subcortical structures. We identify three subcortical regions involved in audio-visual processing of species-specific communicative signal: the amygdala, the claustrum and the pulvinar. Like the cortex, these subcortical structures are not activated when there is a mismatch between visual and acoustic information. In contrast, the amygdala and claustrum are activated by visual, auditory congruent and audio-visual stimulations. The pulvinar responds in a task-dependent manner, along a specific spatial sensory gradient. Anterior pulvinar responds to auditory stimuli, medial pulvinar is activated by auditory, audio-visual and visual stimuli and the dorsal lateral pulvinar only responds to visual stimuli in a pure visual task. The medial pulvinar and the amygdala are the only subcortical structures integrating audio-visual social stimuli. We propose that these three structures belong to a multisensory network that modulates the perception of visual socioemotional information and vocalizations as a function of the relevance of the stimuli in the social context.Significance StatementUnderstanding and correctly associating socioemotional information across sensory modalities, such that happy faces predict laughter and escape scenes screams, is essential when living in complex social groups. Using functional magnetic imaging in the awake macaque, we identify three subcortical structures – amygdala, claustrum and pulvinar - that only respond to auditory information that matches the ongoing visual socioemotional context, such as hearing positively valenced coo calls and seeing positively valenced grooming monkeys. We additionally describe task-dependent activations in the pulvinar, organizing along a specific spatial sensory gradient, supporting its role as a network regulator.
Fluorescence lifetime enables high-resolution analysis of neuromodulator dynamics across time and animals
Authors: Ma Pingchuan , Chen Peter , Tilden Elizabeth , Aggarwal Samarth , Oldenborg Anna , Chen Yao 
Published: September 2022

ABSTRACTThe dynamics of neuromodulators are essential for their functions. Optical sensors have transformed the study of neuromodulators because they capture neuromodulator dynamics with high spatial and temporal resolution. However, fluorescence intensity-based sensors are restricted to measure acute changes within one animal over a short period because intensity varies with sensor expression level and excitation light fluctuation. In contrast, fluorescence lifetime is impervious to sensor expression level or excitation light power, allowing comparison between individuals and across long periods. Here, we discover fluorescence lifetime response in multiple intensity-based neuromodulator sensors. Using the acetylcholine sensor GRABACh3.0to investigate the power of lifetime measurement, we find that fluorescence lifetime correlates with animal behavior states accurately despite varying excitation power or changes in sensor expression level across weeks and animals. Thus, fluorescence lifetime of neuromodulator sensors enables comparison of neuromodulator dynamics at high resolution between animals and for chronic time scales.
A simple non-invasive C reactive protein-based score can predict outcome in patients with COVID-19
Authors: Scotto Riccardo , Lanzardo Amedeo , Buonomo Antonio Riccardo , Pinchera Biagio , Letizia Cattaneo , Sardanelli Alessia , Mercinelli Simona , Viceconte Giulio , Zappulo Emanuela , Villari Riccardo , Foggia Maria , Gentile Ivan ,   Federico II COVID-team
Published: September 2022

ABSTRACTBackgroundWe evaluated the role of CRP and other laboratory parameters in predicting the worsening of clinical conditions during hospitalization, ICU admission and fatal outcome among patients with COVID-19.MethodsWe enrolled consecutive adult inpatients with SARS-CoV-2 infection and respiratory symptoms treated in three different COVID centres. We looked for laboratory parameters collected within 48 hours from hospital admission as predictors of clinical condition.ResultsThree-hundred ninety patients were included in the study. At the correlation and regression analysis, age, baseline CRP and LDH were associated with a P/F ratio<200 during hospitalization. At the multivariate analysis, male gender and CRP > 60 mg/l at admission showed to be independently associated with ICU admission. Lymphocytes<1000 cell/μL at admission were associated with worst P/F ratio. The only laboratory predictor of fatal outcome was CRP>60 mg/l at admission. Based on these results, we devised an 11-points numeric ordinary score based on age, sex, CRP and LDH at admission (ASCL score). Patients with ASCL score of 0 or 2 showed to be protected against a P/F ratio<200, while patients with ASCL score of 6, 7 and 8 showed to be at risk for P/F ratio<200. Patients with ASCL score≥7 had a significant increase to die during the hospitalization.ConclusionsPatients with CRP>60 mg/l or LDH>300 IU/l at hospital admission, as well as patients with an ASCL score>6 at hospital admission, should be prioritized for careful respiratory function monitoring and early treatment to prevent a progression of the disease.
Production of selenium nanoparticles occurs through an interconnected pathway of sulfur metabolism and oxidative stress response inPseudomonas putidaKT2440
Authors: Avendaño Roberto , Muñoz-Montero Said , Rojas-Gätjens Diego , Fuentes Paola , Vieto Sofía , Montenegro Rafael , Salvador Manuel , Frew Rufus , Kim Juhyun , Chavarría Max , Jiménez Jose I. 
Published: September 2022

AbstractThe soil bacteriumPseudomonas putidaKT2440 has been shown to produce selenium nanoparticles aerobically from selenite; however, the molecular actors involved in this process are unknown. Here, through a combination of genetic and analytical techniques, we report the first insights into selenite metabolism in this bacterium. Our results suggest that the reduction of selenite occurs through an interconnected metabolic network involving central metabolic reactions, sulfur metabolism, and the response to oxidative stress. Genes such assucA, D2HGDH and PP_3148 revealed that the 2-ketoglutarate and glutamate metabolism is important to converting selenite into selenium. On the other hand, mutants affecting the activity of sulfite reductase reduced the bacteria’s ability to transform selenite. Other genes related to sulfur metabolism (ssuEF,sfnCE, sqrR,sqrandpdo2) and stress response (gqr,lsfA,ahpCFandsadI) were also identified as involved in selenite transformations. Interestingly, suppression of genessqrR,sqrandpdo2resulted in the production of selenium nanoparticles at a higher rate than the wild-type strain, which is of biotechnological interest. The data provided in this study brings us closer to understanding the metabolism of selenium in bacteria, and offers new targets for the development of biotechnological tools for the production of selenium nanoparticles.
Location of CD39+ T cell sub-populations within tumours predict differential outcomes in non-small cell lung cancer
Authors: Koppensteiner Lilian , Mathieson Layla , Pattle Samuel , Dorward David A , O’Connor Richard , Akram Ahsan 
Published: September 2022

AbstractAn improved mechanistic understanding of immunosuppressive pathways in NSCLC is important to develop novel diagnostic and therapeutic approaches. Here, we reveal that the prognostic significance of the rate limiting ectonucleotidases in adenosine production CD39 and CD73 requires knowledge of cell type specific expression and localisation within tumours. In a cohort of early treatment naïve NSCLC patients, high stromal expression of CD39 and CD73 predicts poor outcome. CD39 expression amongst T cells identifies CD39+CD4+ Tregs which predict poor outcome and CD39+CD103+ CTL which confer a survival benefit if high densities are observed inside of the tumour nest. Bulk RNA Seq shows that the TME of NSCLC upregulates regulatory pathways in CD4+ T cells and exhaustion in CD8+ T cells. Analysis of single-cell RNASeq datasets illustrates that CD39+CD4+ Tregs are enriched in Treg signature gene sets, and CD39+CD103+ CTL show gene signatures indicative of an exhausted cytotoxic phenotype with an upregulated expression of CXCL13.Combined knowledge of patterns of distribution and location are required to understand the prognostic impact of CD39+ T cell populations in NSCLC. This study provides an improved understanding of the spatial and functional characteristics of CD39+ T cells and illustrates their significance to patient outcome.
Lineage segregation in human pre-implantation embryos is specified by YAP1 and TEAD1
Authors: Regin Marius , Essahib Wafaa , Demtschenko Andrej , Dewandre Delphine , David Laurent , Gerri Claudia , Niakan Kathy , Verheyen Greta , Tournaye Herman , Sterckx Johan , Sermon Karen , Van de Velde Hilde 
Published: September 2022

ABSTRACTWe know that polarity and YAP1 play a key role in trophectoderm initiation in compacted human embryos, however we know little about the TEAD family of transcription factors that become activated by YAP1 and especially if they play a role during epiblast and primitive endoderm formation. Here we show that compaction occurs heterogeneously between the 8- and 16-cell stages. While 8-cell stage blastomeres are not yet polarized, polarized outer cells and non-polarized inner cells arise in compacted 16-cell stage embryos. While trophectoderm specifiers TEAD1, YAP1 and GATA3 mostly co-localise in the nuclei of polarized outer/trophectoderm cells, they are also found in some cells of compacting embryos before polarity is established indicating that differentiation into trophectoderm cells can be initiated independently of polarity. In the inner cell mass, TEAD1 and YAP1 also distinguish GATA4 positive cells in a salt-and-pepper distribution and in the sorted primitive endoderm cells. Our detailed roadmap on polarization, compaction, position and lineage segregation events during human preimplantation development paves the road for further functional studies. Fundamental knowledge of lineage segregation events will eventually explain how and why embryos fail to develop further before or during implantation.
Including both sexes in in vivo research does not necessitate an increase in sample size: a key role for factorial analysis methods
Authors: Phillips Benjamin , Haschler Timo N. , Karp Natasha A. 
Published: September 2022

AbstractIn recent years, there has been a strong drive to improve the inclusion of animals of both sex during in vivo research, driven by a need to improve sex representation in fundamental biology and drug development. This has resulted in inclusion mandates by funding bodies and journals, alongside numerous published manuscripts highlighting the issue and providing guidance to scientists. However, progress is slow and blockers to the routine use of both sexes remain. From a statistical and experimental design perspective, concerns include difficulty selecting and conducting an appropriate analysis and the perceived need for a higher sample size to achieve an equivalent level of statistical power. When both sexes are included, analysis errors are frequent, including inappropriate pooling or sex-disaggregation of the data. These mistakes result in a failure to properly account for the variation in the data that arises from sex, and subsequently lead to poor inference regarding the biological impact of sex. The purpose of this manuscript is to address frequently cited blockers and analysis errors, thus providing a practical guide to support scientists in the design of in vivo studies which include both sexes. Primarily, we demonstrate that there is no loss of power to detect treatment effects when splitting the sample size across sexes in most common biological scenarios, providing that the data are analysed appropriately. In the rare situations where power is lost, the benefit of understanding the role of sex outweighs the power considerations. When estimating a generalisable translatable effect, where exploring sex differences are not the primary scientific objective, we recommend splitting the sample size across male and female mice as a standard strategy. We also demonstrate an optimal analysis pipeline for analysing data gathered using both sexes which is designed to help address common analysis errors.
MicroRNA-335-5p suppresses voltage-gated sodium channel expression and may be a target for seizure control
Authors: Heiland Mona , Connolly Niamh M. C. , Nguyen Ngoc T. , Kesavan Jaideep C. , Fanning Kevin , Sanfeliu Albert , Yan Yan , Venø Morten T. , Costard Lara S. , Neubert Valentin , Hill Thomas D. M. , Rosenow Felix , Bauer Sebastian , Kjems Jørgen , Morris Gareth , Henshall David C. 
Published: September 2022

AbstractThere remains an urgent need for new therapies for drug-resistant epilepsy (DRE). Sodium channel blockers are effective for seizure control in common forms of epilepsy, but loss of sodium channel function underlies some genetic forms of epilepsy. Approaches that provide bi-directional control of sodium channel expression are needed. MicroRNAs (miRNA) are small non-coding RNAs which negatively regulate gene expression. Here, we show that genome-wide miRNA screening of hippocampal tissue from a rat epilepsy model, mice treated with the novel anti-seizure medicine cannabidiol (CBD) and plasma from patients with DRE, converge on a single target, miR-335-5p. Pathway analysis on predicted and validated miR-335-5p targets identified multiple voltage-gated sodium channels (VGSCs). Intracerebroventricular injection of antisense oligonucleotides against miR-335-5p resulted in upregulation of Scn1a, Scn2a and Scn3a in the mouse brain and an increased action potential rising phase and greater excitability of hippocampal pyramidal neurons in brain slice recordings, consistent with VGSCs as functional targets of miR-335-5p. Blocking of miR-335-5p also increased voltage-gated sodium currents in human iPSC-derived neurons. Inhibition of miR-335-5p increased susceptibility to tonic-clonic seizures in the pentylenetetrazole seizure model, whereas AAV9-mediated overexpression of miR-335-5p reduced seizure severity and improved survival. These studies suggest modulation of miR-335-5p may be a means to regulate VGSCs and affect brain excitability and seizures. Changes to miR-335-5p may reflect compensatory mechanisms to control excitability and could provide new biomarker or therapeutic strategies for different types of drug-resistant epilepsy.Significance StatementDespite the clinical availability of over 30 anti-seizure medications (ASMs), around 30% of people with epilepsy do not achieve seizure freedom. MicroRNAs are small non-coding RNAs which negatively regulate protein expression by binding to target mRNAs. Here, we identified the brain-enriched miR-335-5p to be commonly altered in three heterogenous miRNA profiling datasets. Bi-directional modulation of miR-335-5p identified a potential homeostatic role of miR-335-5p in brain excitability involving voltage-gated sodium channels. Electrophysiological and in vivo approaches revealed pro-epileptic activity of miR-335-5p inhibition whereas overexpression of miR-335-5p resulted in anti-epileptic activity. Overall, targeting miR-335-5p could provide a new approach in the modulation of brain excitability, with possible therapeutic applications in drug-resistant epilepsies and other neurological diseases.
Structural and functional characterization of chloroplast ribulose-5-phosphate-3-epimerase from the model green microalgaChlamydomonas reinhardtii
Authors: Meloni Maria , Fanti Silvia , Tedesco Daniele , Gurrieri Libero , Trost Paolo , Fermani Simona , Lemaire Stéphane D. , Zaffagnini Mirko , Henri Julien 
Published: September 2022

AbstractPhotosynthetic carbon fixation relies on Rubisco and ten additional enzymes in the conserved Calvin-Benson-Bassham (CBB) cycle. Epimerization of xylulose-5-phosphate (X5P) into ribulose-5-phosphate (Ru5P) contributes to the regeneration of ribulose-1,5-bisphosphate, the substrate of Rubisco activity. Ribulose-5-phosphate-3-epimerase (RPE) catalyzes the formation of Ru5P but it can also operate in the pentose phosphate pathway (PPP) by catalyzing the reverse reaction. Here, we describe the catalytic and structural properties of the recombinant form of photosynthetic RPE isoform 1 fromChlamydomonas reinhardtii(CrRPE1). The enzyme shows catalytic parameters that are variably comparable to those of the paralogues involved in the PPP and CBB cycle but with some notable exceptions. CrRPE1 is a homo-hexamer that exposes a catalytic pocket on the top of anα8β8triose isomerase-type (TIM-) barrel as observed in structurally solved RPE isoforms from both plant and non-plant sources. Despite being identified as a putative target of thiol-based redox modifications, CrRPE1 activity is not altered by redox treatments, indicating that the enzyme does not bear redox sensitive thiol groups and is not regulated by thiol-switching mechanisms. We mapped phosphorylation sites on the crystal structure and the specific location at the entrance of the catalytic cleft supports a phosphorylation-based regulatory mechanism. Overall, this work provides a detailed description of the catalytic and regulatory properties of CrRPE along with structural data, which allow for a deeper understanding of the functioning of this enzyme of the CBB cycle and in setting the basis for possible strategies to improve the photosynthetic metabolism.
Towards environmental detection, quantification, and molecular characterization of Anopheles stephensi and Aedes aegypti from larval breeding sites
Authors: Kristan Mojca , Acford-Palmer Holly , Campos Monica Oliveira , Collins Emma , Phelan Jody , Portwood Natalie M. , Pelloquin Bethanie , Clarke Sian , Lines Jo , Clark Taane G. , Walker Thomas , Campino Susana , Messenger Louisa A. 
Published: September 2022

AbstractThe invasion and establishment of An. stephensi mosquitoes in the Horn of Africa represents a significant regional threat, which may jeopardise malaria control, particularly in urban areas which were formally free from disease transmission. Novel vector surveillance methods are urgently needed, both agnostic to mosquito larval morphology, and simple to implement at the sampling stage. Using new multiplex TaqMan assays, specifically targeting An. stephensi and Ae. aegypti, we validated the use of environmental DNA (eDNA) for simultaneous vector detection in shared artificial breeding sites. Study findings demonstrated that An. stephensi and Ae. aegypti eDNA deposited by as few as one second instar larva in 1L of water was detectable. Characterization of molecular insecticide resistance mechanisms, using novel amplicon-sequencing panels for both vector species, was possible from eDNA shed by as few as 32 second instar larvae in 50ml of water. An. stephensi eDNA, derived from emergent pupae for 24 hours, was remarkably stable, and still detectable ~2 weeks later. eDNA surveillance has the potential to be implemented in local endemic communities and points of country entry, to monitor the spread of invasive vector species. Further studies are required to validate the feasibility of this technique under field conditions.
LKB1 regulates JNK-dependent stress signaling and apoptotic dependency ofKRAS-mutant lung cancers
Authors: Li Chendi , Syed Mohammed Usman , Nimbalkar Anahita , Shen Yi , Fraser Cameron , Inde Zintis , Qin Xingping , Ouyang Jian , Kreuzer Johannes , Clark Sarah E. , Kelley Grace , Hensley Emily , Morris Robert , Lazaro Raul , Belmontes Brian , Oh Audris , Walcott Makeba , Nabel Christopher , Caenepeel Sean , Saiki Anne Y. , Rex Karen , Lipford J. Russell , Heist Rebecca S. , Lin Jessica J. , Haas Wilhelm , Sarosiek Kristopher , Hughes Paul E. , Hata Aaron N. 
Published: September 2022

AbstractThe efficacy of molecularly targeted anti-cancer therapies may be limited by the presence of co-occurring mutations within a tumor1–3. Conversely, these alterations may confer collateral vulnerabilities that can be leveraged for the development of novel therapeutic approaches.KRAS-mutant lung cancers are distinguished by recurrent inactivating mutations in the tumor suppressorSTK11/LKB14that facilitate tumorigenesis by modulating energy balance5, 6, enhancing metastatic potential7,8and enabling immune evasion9,10. However, whether LKB1 plays a role in modulating cellular responses to therapeutic stress is largely unknown. Here we show that LKB1 suppresses JNK-dependent stress signaling inKRAS-mutant lung cancer cells upon acute loss of oncogenic signaling. In LKB1-deficientKRAS-mutant cells, inhibition of KRAS or its downstream effector MEK leads to hyperactivation of JNK due to loss of NUAK-mediated PP1B phosphatase activity. JNK-mediated inhibitory phosphorylation of BCL-XL rewires apoptotic dependencies, rendering LKB1-deficient cells vulnerable to MCL-1 inhibition. These results uncover a previously unknown role for LKB1 in regulating stress signaling and the mitochondrial apoptotic response of cancer cells independent of its tumor suppressor activity mediated by AMPK11–13and SIK14,15kinases. Additionally, our study reveals a therapy-induced vulnerability in LKB1-deficientKRAS-mutant lung cancer cells that could be exploited as a genotype-informed strategy to improve the efficacy of KRAS-targeted therapies.
Modeling Microtubule-Cytoplasm Interaction in Plant Cells
Authors: Murshed Mohammad , Wei Donghui , Gu Ying , Wang Jin 
Published: September 2022

AbstractAlthough microtubules in plant cells have been extensively studied, the mechanisms that regulate the spatial organization of microtubules are poorly understood. We hypothesize that the interaction between microtubules and cytoplasmic flow plays an important role in the assembly and orientation of microtubules. To test this hypothesis, we developed a new computational modeling framework for microtubules based on theory and methods from the fluid-structure interaction. We employed the immersed boundary method to track the movement of microtubules in cytoplasmic flow. We also incorporated details of the encounter dynamics when two microtubules collide with each other. We verified our computational model through several numerical tests before applying it to the simulation of the microtubule-cytoplasm interaction in a growing plant cell. Our computational investigation demonstrated that microtubules are primarily oriented in the direction orthogonal to the axis of cell elongation. We validated the simulation results through a comparison with the measurement from laboratory experiments. We found that our computational model, with further calibration, was capable of generating microtubule orientation patterns that were qualitatively and quantitatively consistent with the experimental results. The computational model proposed in this study can be naturally extended to many other cellular systems that involve the interaction between microstructures and the intracellular fluid.