bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hearing elliptic movements reveals the imprint of action on prototypical geometries
Authors: Thoret Etienne , Aramaki Mitsuko , Bringoux Lionel , Ystad Sølvi , Kronland-Martinet Richard 
Published: November 2022

AbstractWithin certain categories of geometric shapes, prototypical exemplars that best characterize the category have been evidenced. These geometric prototypes are classically identified through the visual and haptic perception or motor production and are usually characterized by their spatial dimension. However, whether prototypes can be recalled through the auditory channel has not been formally investigated. Here we address this question by using auditory cues issued from timbre-modulated friction sounds evoking human drawing elliptic movements. Since non-spatial auditory cues were previously found useful for discriminating distinct geometric shapes such as circles or ellipses, it is hypothesized that sound dynamics alone can evoke shapes such as an exemplary ellipse. Four experiments were conducted and altogether revealed that a common elliptic prototype emerges from auditory, visual, and motor modalities. This finding supports the hypothesis of a common coding of geometric shapes according to biological rules with a prominent role of sensory-motor contingencies in the emergence of such prototypical geometry.
Historical use of coastal wetlands by small-scale fisheries in the Northern Gulf of California
Authors: Morzaria-Luna Hem Nalini , Urquidi Mabilia , Cruz-Piñón Gabriela , Dorantes Hernández Jośe Manuel , Valdivia Jiménez Paloma A. , Cruz Ángeles Sánchez , Martínez Ilse 
Published: November 2022

AbstractCoastal wetlands are rich and productive ecosystems that historically have been used by small-scale fisheries due to their role as refuges, feeding, and nursery habitats for commercial target species. We used wetland resource users’ Local Ecological Knowledge to document historical patterns of commercial species abundance, areas of fishing importance, trophic level, and species richness and composition in coastal wetlands in the Northern Gulf of California, Mexico. We also reconstructed the environmental history of coastal wetlands in this region from bibliographic sources and photographic records, to document impacts that could have affected coastal fisheries. We found a consistent downward trend in target species abundance; the decrease was perceived as more pronounced by fishers that began fishing in or prior to the 1950’s, pointing to shifting baselines, the failure for resource users to recognize environmental change and accept degraded states as normal. Areas of fishing importance within coastal wetlands also decreased through time. Trophic level of catch showed no distinct pattern across wetland sites or time. Perceived species richness and composition increased with wetland size. Our analysis of the small-scale use of coastal wetlands in the Northern Gulf is relevant to food security and can provide insight into how local populations adapt to depleted coastal food webs.
The aminoglycoside streptomycin triggers ferroptosis in tumor initiating cells
Authors: Guillorit Hélène , Relier Sébastien , Zagiel Benjamin , Di Giorgio Audrey , Cazevieille Chantal , Bansard Lucile , Bouclier Céline , Mialhe Xavier , Brisset Morgan , Hideg Szimonetta , Choquet Armelle , Planque Chris , Bastide Amandine , Pannequin Julie , Duca Maria , Macari Françoise , David Alexandre 
Published: November 2022

ABSTRACTCompelling evidence suggests that tumor initiating cells (TIC) are the roots of current shortcomings in advanced and metastatic cancer treatment. TIC represents a minor subpopulation of tumor cells endowed with self-renewal and multi-lineage differentiation capacity, which can disseminate and seed metastasis in distant organ. Our work identified Streptomycin (SM), a potent bactericidal antibiotic, as a new molecule capable of targeting non-adherent TIC from colon and breast cancer cell lines by inducing mitochondrial-dependent ferroptosis. SM-induced ferroptosis associates with profound alterations in mitochondrial morphology, such as swelling and cristae enlargement, coupled with hyperpolarization of mitochondrial membrane potential and production of mitochondrial ROS. The peculiar SM structure, and more particularly its aldehyde group, is essential for this mechanism. As such, the mere reduction of SM into dihydrostreptomycin abolishes its effect on TIC. This study reveals a new mechanism of action of SM that could help comprehend the molecular basis of TIC adaptation to inhospitable environments and pave the way for new treatment of advanced cancers.
Capturing species-wide diversity of the gut microbiota and its relationship with genomic variation in the critically endangered kākāpō
Authors: West Annie G. , Digby Andrew , Santure Anna W. , Guhlin Joseph G. , Dearden Peter ,   Kākāpō Recovery Team, Taylor Michael W. , Urban Lara 
Published: November 2022

AbstractThe gut microbiota plays an essential role in host health that has important implications for the conservation management of threatened wildlife. While factors such as diet, medication, and habitat are known to shape the microbiota, our understanding of the entirety of factors, including the complex role of the host genomic background, remains incomplete. Our research on the gut microbiota of the critically endangered kākāpō (Strigops habroptilus), a flightless parrot species endemic to Aotearoa New Zealand, represents, to our knowledge, the first study to describe the gastrointestinal bacterial diversity for virtually an entire species and to assess the relationship between gut microbiota and host genomic diversity in a highly threatened population. Here we report a 16S rRNA gene-based analysis of kākāpō faecal samples representing the gut microbiota for 84% of kākāpō (n = 133). This survey was then leveraged with exceptional metadata to tease apart the impact of host genomic diversity and factors such as sex, diet, antibiotic treatment, disease status, habitat, and time of sampling on the kākāpō gut microbiota, with sex being the only covariate significantly associated with gut microbiota diversity. We find evidence of a highly polygenic genomic architecture of the gut microbiota and further identify putative associations between gut bacterial diversity and functional biological pathways related to intestinal homeostasis, inflammation, immune response and metabolism. This improved understanding of the kākāpō gut microbiota – and its relationship with host genomics – can directly benefit kākāpō management and conservation by providing new insights into the role of the gut microbiome in kākāpō health and disease mitigation. Overall, we anticipate that an integration of microbiome studies in conservation research and management will improve our understanding of how the concept of One Health with its implications for human, animal and environmental welfare can be achieved.
Systematic analysis of cell morphodynamics inC. elegansearly embryogenesis
Authors: Azuma Yusuke , Okada Hatsumi , Onami Shuichi 
Published: November 2022

AbstractThe invariant cell lineage ofCaenorhabditis elegansallows unambiguous assignment of the identity for each cell, which offers a unique opportunity to study developmental dynamics such as the timing of cell division, dynamics of gene expression, and cell fate decisions at single-cell resolution. However, little is known about the cell morphodynamics, including the extent to which they are variable between individuals, mainly due to the lack of sufficient amount and quality of quantified data. In this study, we systematically quantified the cell morphodynamics in 52C. elegansembryos from the two-cell stage to mid-gastrulation at high spatiotemporal resolution, 0.5 μm thickness of optical sections, and 30-second intervals of recordings. By comparing the morphodynamics between the embryos, we found high reproducibility of the dynamics. The median correlation coefficient of morphological features, such as volume and surface area, was 0.09, suggesting high reproducibility. Furthermore, the morphodynamics was significantly different from the other cell types in all cells before the onset of gastrulation, indicating high uniqueness of the dynamics. Furthermore, physical cell-cell contacts were quantified to analyze inter-cell relationships, and their reproducibility was calculated between the embryos. The number of contacts formed in every embryo was less than half of all detected contacts because variability in division timings and cell arrangements produced various combinations of brief contacts. In contrast, the area of contacts formed in every embryo occupied 96% of the total area, suggesting the high reproducibility of spatial occupancies and adjacency relationships of the cells. Our data further allowed detailed analyses of specific cellular features. By normalizing the sphericity dynamics, we found a significant increase in sphericity at the end of metaphase in every cell, indicating the universality of the mitotic cell rounding. Concomitant with the rounding, the volume also increased in most but not all cells, suggesting less universality of the mitotic swelling. Therefore, we demonstrate that our data provides a precise understanding of the cellular processes and could potentially be used to gain further insight into developmental mechanisms.
Transient receptor potential melastatin 4 (TRPM4) regulates hilar mossy cell loss in temporal lobe epilepsy
Authors: Mundrucz Laura , Kecskés Angéla , Henn-Mike Nóra , Kóbor Péter , Buzás Péter , Vennekens Rudi , Kecskés Miklós 
Published: November 2022

ABSTRACTMossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients, however the mechanisms leading to cellular death is unclear. One possible explanation for their sensitivity is linked to their specific ion channel composition. TRPM4 is a Ca2+-activated non-selective cation channel regulating diverse physiological function of excitable cells. Here, we identified that TRPM4 is present and functionally active in hilar mossy cells. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits in the chronic phase of TLE.
Optogenetic control of beta-carotene bioproduction in yeast across multiple lab-scales
Authors: Pouzet Sylvain , Cruz-Ramon Jessica , Bec Matthias Le , Cordier Céline , Banderas Alvaro , Barral Simon , Sorre Benoit , Castano-Cerezo Sara , Lautier Thomas , Truan Gilles , Hersen Pascal 
Published: November 2022

ABSTRACTOptogenetics arises as a valuable tool to precisely control genetic circuits in microbial cell factories. Light control holds the promise of optimizing bioproduction methods and maximize yields, but its implementation at different steps of the strain development process and at different culture scales remains challenging. In this study, we aim to control beta-carotene bioproduction using optogenetics inSaccharomyces cerevisiaeand investigate how its performance translates across culture scales. We built four lab-scale illumination devices, each handling different culture volumes, and each having specific illumination characteristics and cultivating conditions. We evaluated optogenetic activation and beta-carotene production across devices and optimized them both independently. Then, we combined optogenetic induction and beta-carotene production to make a light-inducible beta-carotene producer strain. This was achieved by placing the transcription of the bifunctional lycopene cyclase / phytoene synthase CrtYB under the control of the pC120 optogenetic promoter regulated by the EL222-VP16 light-activated transcription factor, while other carotenogenic enzymes (CrtI, CrtE, tHMG) were expressed constitutively. We show that illumination, culture volume and shaking impact differently optogenetic activation and beta-carotene production across devices. This enabled us to determine the best culture conditions to maximize light-induced beta-carotene production in each of the devices, reaching a content of up to 880 μg/gCDW. Our study exemplifies the stakes of scaling up optogenetics in devices of different lab scales and sheds light on the interplays and potential conflicts between optogenetic control and metabolic pathway efficiency. As a general principle, we propose that it is important to first optimize both components of the system independently, before combining them into optogenetic producing strains to avoid extensive troubleshooting. We anticipate that our results can help designing both strains and devices that could eventually lead to larger scale systems in an effort to bring optogenetics to the industrial scale.
Online versus Cognitive Control: A Dividing Line between Physical Action and Motor Imagery
Authors: Martel Marie , Glover Scott 
Published: November 2022

AbstractRecent work has shown that motor imagery is highly sensitive to tasks that interfere with executive resources, whereas physical actions are largely immune. This has been taken as support for the Motor-Cognitive model of motor imagery, and against the theory of Functional Equivalence. Here, we examined another prediction of the MCM, namely that an opposite pattern of effects would be observed when the information available for online control was reduced. This was tested in three experiments in which participants performed either physical actions or motor imagery. The experiments manipulated the quality of information available during the online control of movement through: 1) comparing movements made with or without visual feedback; 2) comparing movements made using foveal vs. peripheral vision; and 3) comparing physical to mimed actions. All three experiments found evidence in favour of the Motor-Cognitive model in that manipulations of online control affected motor imagery but not overt action. These same results were, however, inconsistent with a Functional Equivalence view. We discuss these results in the broader context of theoretical views on perceptual vs. motor imagery.
Interactions between Trypillian farmers and North Pontic forager-pastoralists in Eneolithic central Ukraine
Authors: Nikitin Alexey G. , Videiko Mykhailo , Patterson Nick , Renson Virginie , Reich David 
Published: November 2022

AbstractThe establishment of agrarian economy in Eneolithic East Europe is associated with the Pre-Cucuteni-Cucuteni-Trypillia complex (PCCTC). PCCTC farmers interacted with Eneolithic forager-pastoralist groups of the North Pontic steppe as PCCTC extended from the Carpathian foothills to the Dnipro Valley beginning in the late 5thmillennium BCE. While the cultural interaction between the two groups is evident through the Cucuteni C pottery style that carries steppe influence, the extent of biological interactions between Trypillian farmers and the steppe remains unclear. Here we report the analysis of artefacts from the late 5thmillennium Trypillian site of Kolomiytsiv Yar Tract (KYT) in central Ukraine, focusing on a bone fragment found in the Trypillian context at KYT. Diet stable isotope ratios obtained from the bone fragment place the diet of the KYT individual within the range of forager-pastoralists of the North Pontic area. Strontium isotope ratios of the KYT individual are consistent with having originated from contexts of the Sredny Stog culture sites of the Middle Dnipro Valley. Genetic analysis of the KYT individual indicates ancestry derived from a proto-Yamna population such as Sredny Stog. Overall, the KYT archaeological site presents evidence of interactions between Trypillians and Eneolithic Pontic steppe inhabitants of the Sredny Stog horizon and suggests a potential for gene flow between the two groups as early as the beginning of the 4thmillennium BCE.
Dually biofortified cisgenic tomatoes with increased flavonoids and branched-chain amino acids content
Authors: Vazquez-Vilar Marta , Fernandez-del-Carmen Asun , Garcia-Carpintero Victor , Drapal Margit , Presa Silvia , Ricci Dorotea , Diretto Gianfranco , Rambla José Luis , Fernandez-Muñoz Rafael , Espinosa-Ruiz Ana , Fraser Paul D. , Martin Cathie , Granell Antonio , Orzaez Diego 
Published: November 2022

AbstractHigher dietary intakes of flavonoids may have a beneficial role in cardiovascular disease prevention. Additionally, supplementation of branched-chain amino acids (BCAAs) in vegan diets can reduce risks associated to their deficiency, particularly in older adults, which can cause loss of skeletal muscle strength and mass. Most plant-derived foods contain only small amounts of BCAAs and those plants with high levels of flavonoids are not eaten broadly. Here we describe the generation of metabolically-engineered cisgenic tomatoes enriched in both flavonoids and BCAAs. In this approach, coding and regulatory DNA elements, all derived from the tomato genome, were combined to obtain a herbicide-resistant version of an acetolactate synthase (mSlALS) gene expressed broadly, and a MYB12-like transcription factor (SlMYB12) expressed in a fruit-specific manner. The mSlALS played a dual role, as a selectable marker as well as being key enzyme in BCAA enrichment. The resulting cisgenic tomatoes were highly enriched in Leucine (21-fold compared to wild type levels), Valine (9-fold), Isoleucine (3-fold), and concomitantly biofortified in several antioxidant flavonoids including kaempferol (64-fold) and quercetin (45-fold). Comprehensive metabolomic and transcriptomic analysis of the biofortified cisgenic tomatoes revealed marked differences to wild type and could serve to evaluate the safety of these biofortified fruits for human consumption.
GluK2 Q/R editing regulates kainate receptor signalling to modulate AMPA receptor synaptic expression and plasticity
Authors: Nair Jithin D. , Wilkinson Kevin A. , Yucel Busra P. , Mulle Christophe , Vissel Bryce , Mellor Jack , Henley Jeremy M. 
Published: November 2022

SummaryQ/R editing of the kainate receptor (KAR) subunit GluK2 radically alters properties of recombinant KARs, but the effectsin vivoremain largely unexplored. We compared GluK2 editing-deficient mice that express ∼95% unedited GluK2(Q) to wild-type counterparts that express ∼85% edited GluK2(R). At mossy fibre-CA3 (MF-CA3) synapses GluK2(Q) mice displayed enhanced postsynaptic KAR function and increased KAR-mediated presynaptic facilitation, demonstrating heightened ionotropic function. Conversely, there was reduced metabotropic KAR function, assessed by KAR-mediated afterhyperpolarization currents, in GluK2(Q) mice. GluK2(Q) mice had fewer GluA1- and GluA3-containing AMPA receptors (AMPARs) and reduced postsynaptic AMPAR currents at both MF-CA3 and CA1-Schaffer collateral synapses. Moreover, long-term potentiation of AMPAR-mediated transmission at CA1-Schaffer collateral synapses was reduced in GluK2(Q) mice. These findings suggest that GluK2 Q/R editing influences ionotropic/metabotropic balance of KAR signalling to regulate synaptic expression of AMPARs and plasticity.
Synchronized proinsulin trafficking reveals delayed Golgi export accompanies β-cell secretory dysfunction in a rodent model of hyperglycemia
Authors: Boyer Cierra K. , Bauchle Casey J. , Zhang Jianchao , Wang Yanzhuang , Stephens Samuel B. 
Published: November 2022

SummaryThe pancreatic islet β-cell’s preference for release of newly synthesized insulin requires careful coordination of insulin exocytosis with sufficient insulin granule production to ensure that insulin stores exceed peripheral demands for glucose homeostasis. Thus, the cellular mechanisms regulating insulin granule production are critical to maintaining β-cell function. In this report, we utilized the synchronous protein trafficking system, RUSH, in primary β-cells to evaluate proinsulin transit through the secretory pathway leading to insulin granule formation. We demonstrate that the trafficking, processing, and secretion of the proinsulin RUSH reporter, proCpepRUSH, are consistent with current models of insulin maturation and release. Using a rodent dietary model of hyperglycemia and β-cell dysfunction, we show that proinsulin trafficking is impeded at the Golgi and coincides with the decreased appearance of nascent insulin granules at the plasma membrane. Ultrastructural analysis of β-cells from diabetic leptin receptor deficient mice revealed gross morphological changes in Golgi structure, including shortened and swollen cisternae, and partial Golgi vesiculation, which are consistent with defects in secretory protein export. Collectively, this work highlights the utility of the proCpepRUSH reporter in studying proinsulin trafficking dynamics and suggests that altered Golgi export function contributes to β-cell secretory defects in the pathogenesis of Type 2 diabetes.
The Transcription Factor Foxi1 Promotes Expression of V-ATPase and Gpr116 in M-1 cells
Authors: Kui Mackenzie , Pluznick Jennifer L. , Zaidman Nathan A. 
Published: November 2022

AbstractThe diverse functions of each nephron segment rely on the coordinated action of specialized cell populations that are uniquely defined by their transcriptional profile. In the collecting duct, there are two critical and distinct cell populations: principal cells and intercalated cells. Principal cells play key roles in the regulation of water, Na+, and K+, while intercalated cells are best known for their role in acid-base homeostasis. Currently, there are noin vitrosystems that recapitulate the heterogeneity of the collecting ducts, which limits high-throughput and replicate investigations of genetic and physiological phenomena. Here, we have demonstrated that the transcription factor Foxi1 is sufficient to alter the transcriptional identity of M-1 cells, a murine cortical collecting duct cell line. Specifically, overexpression ofFoxi1induces the expression of intercalated cell transcripts includingGpr116, Atp6v1b1, Atp6v1g3, Atp6v0d2, Slc4a9, andSlc26a4. These data indicate that overexpression ofFoxi1differentiates M-1 cells towards a B-type intercalated cell phenotype and may provide a novelin vitrotool to study transcriptional regulation and physiological function of the renal collecting duct.
Allosteric inhibition of the epidermal growth factor receptor through disruption of transmembrane interactions
Authors: Rybak Jennifer A , Sahoo Amita R , Kim Soyeon , Pyron Robert J , Pitts Savannah B , Guleryuz Saffet , Smith Adam W , Buck Matthias , Barrera Francisco N 
Published: November 2022

AbstractThe epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) commonly targeted for inhibition by anti-cancer therapeutics. Current therapeutics target EGFR’s kinase domain or extracellular region. However, these types of inhibitors are not specific for tumors over healthy tissue and therefore cause undesirable side effects. Our lab has recently developed a new strategy to regulate RTK activity by designing a peptide that specifically binds to the transmembrane (TM) region of the RTK to allosterically modify kinase activity. These peptides are acidity-responsive, allowing them to preferentially target acidic environments like tumors. We have applied this strategy to EGFR and created the PET1 peptide. We observed that PET1 behaves as a pH-responsive peptide that modulates the configuration of the EGFR TM through a direct interaction. Our data indicated that PET1 inhibits EGFR-mediated cell migration. Finally, we investigated the mechanism of inhibition through molecular dynamics simulations, which showed that PET1 sits between the two EGFR TM helices; this molecular mechanism was additionally supported by AlphaFold-Multimer predictions. We propose that the PET1-induced disruption of native TM interactions disturbs the conformation of the kinase domain in such a way that it inhibits EGFR’s ability to send migratory cell signals. This study is a proof-of-concept that acidity-responsive membrane peptide ligands can be generally applied to RTKs. In addition, PET1 constitutes a viable approach to therapeutically target the TM of EGFR.