bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of bacterial consortia improves seed tuber production in potato varieties for frying
Authors: Mauricio Ramírez Rodrigo , Rodriguez-Grados Pedro , Quiliche Jean Piere , Contreras-Liza Sergio , Montemayor Mantilla José , Palomares Anselmo Edison 
Published: November 2023

AbstractObjectiveTo determine the effect of a consortium of growth-promoting rhizobacteria on potato varieties for frying under controlled conditions.MethodologyThe research was conducted at the Universidad Nacional José Faustino Sánchez Carrión, Huacho, Peru. The experiment was carried out in pots in a greenhouse using a completely randomized design with 6 replications, under a factorial arrangement. Four potato genotypes for frying (cv. Bicentenaria, advanced clones UH-9, CIP 396311.1, CIP 399101.1) and four inoculant treatments were used,Azotobactersp. (T1),Azotobactersp.+Bacillus simplex(T2),Azotobactersp.+B. subtilis(T3),Azotobactersp.+B. subtilis+B. simplex(T4) and an uninoculated control (T0). The variables studied were vegetative vigor, plant height, number of stems per plant, number of leaves per plant, fresh and dry weight per plant, tuber diameter, and number and weight of tubers per plant. Data were statistically processed and analysed by performing Scott-Knott’s comparison of treatments and using principal component analysis.ResultsThe inoculation alone withAzotobactersp. (T1) or with the consortiumAzotobactersp.+B. simplex+B. subtilis(T4) significantly promoted potato growth with respect to the number of stems and number of leaves per plant, as well as weight and number of tubers per plant; for vegetative vigor, the control treatment (T0) obtained differences in comparison with the inoculated treatments. Plant height, number of shoots, fresh and dry weight of foliage and tuber diameter did not show significant differences due to the effect of the inoculation. Interactions between varieties and treatments were found for vegetative vigor, the number of leaves and tubers per plant, being positive for the inoculation with some bacterial consortia.ConclusionBacterial consortia withAzotobactersp. promote the growth and productivity of potato varieties for processing under greenhouse conditions.
Aryl amino acetamides prevent the development ofPlasmodium falciparumrings via inhibition of the lipid transfer protein PfSTART1
Authors: Dans Madeline G. , Boulet Coralie , Watson Gabrielle M. , Nguyen William , Dziekan Jerzy M. , Evelyn Cindy , Reaksudsan Kitsanapong , Mehra Somya , Razook Zahra , Geoghegan Niall D. , Mlodzianoski Michael J. , Goodman Christopher Dean , Ling Dawson B. , Jonsdottir Thorey K. , Tong Joshua , Famodimu Mufuliat Toyin , Kouskousis Betty , Delves Michael J. , McFadden Geoffrey I. , Barry Alyssa E. , Crabb Brendan S. , de Koning-Ward Tania F. , Rogers Kelly L. , Cowman Alan F. , Tham Wai-Hong , Sleebs Brad E. , Gilson Paul R. 
Published: November 2023

AbstractWith resistance to most antimalarials increasing, it is imperative that new antimalarial drugs are developed to replace or complement front-line artemisinin therapies. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited ring development of newly invaded merozoites. Here, we selected parasites resistant to M-833 and identified independent mutations arising in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introduction of the identified PfSTART1 mutations into wildtype parasites reproduced resistance to both M-833 and highly potent analogues, confirming PfSTART1 mutations were sufficient to confer resistance. The analogues bound to recombinant PfSTART1 with nanomolar affinity. We also demonstrated selective PfSTART1 engagement by the analogues using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assay for the first time inPlasmodium.Imaging of newly invaded merozoites showed the inhibitors prevented the conversion into larger amoeboid ring-stage parasites potentially through the inhibition of phospholipid transfer from the parasite to the encasing parasitophorous vacuole membrane (PVM) and/or within the parasite. We show that these PfSTART1 inhibitors also block transmission. With multiple stages of the parasite’s lifecycle being targeted by PfSTART1 inhibitors, this protein therefore represents a novel drug target with a new mechanism of action.
Comparative Analysis of GPT-4Vision, GPT-4 and Open Source LLMs in Clinical Diagnostic Accuracy: A Benchmark Against Human Expertise
Authors: Han Tianyu , Adams Lisa C , Bressem Keno , Busch Felix , Huck Luisa , Nebelung Sven , Truhn Daniel 
Published: November 2023

AbstractImportanceMedicine is poised for transformation with artificial general intelligence becoming integral to almost all clinical environments. Currently, the performance of multimodal AI, specifically one powered by GPT-4, in real clinical cases remains uncharted.ObjectiveTo ascertain whether GPT-4V can consistently comprehend complex diagnostic scenarios through both imagery and textual data.DesignA selection of 140 clinical cases from the JAMA Clinical Challenge and 348 from the NEJM Image Challenge were used. Each case, comprising a clinical image and corresponding question, was processed by GPT-4V, and responses were documented. The significance of imaging information was assessed by comparing GPT-4V’s performance with that of four other leading-edge large language models (LLMs).Main Outcomes and MeasuresThe accuracy of responses was gauged by juxtaposing the model’s answers with the established ground truths of the challenges. The confidence interval for the model’s performance was calculated using bootstrapping methods. Additionally, human performance on the NEJM Image Challenge was chronicled, reflected by the choice percentage selected by challenge participants.ResultsGPT-4V demonstrated superior accuracy in analyses of both sources, achieving 73.3% for JAMA and 88.7% for NEJM, notably outperforming text- only LLMs such as GPT-4, GPT-3.5, Llama2, and Med-42. Remarkably, both GPT-4V and GPT-4 exceeded average human participants’ performance at all complexity levels within the NEJM Image Challenge.Conclusions and RelevanceGPT-4V has exhibited considerable promise in clinical diagnostic tasks, surpassing the capabilities of its predecessors as well as those of human experts. However, while its proficiency in identification tasks is commendable, it requires further refinement in decision-making and strategic planning. Despite these encouraging results, such models should be adopted with prudence in clinical settings, serving to augment rather than replace human discretion. Continual research is imperative to fully evaluate the potential impact on patient care.
An integrated single-cell reference atlas of the human endometrium
Authors: Marečková Magda , Garcia-Alonso Luz , Moullet Marie , Lorenzi Valentina , Petryszak Robert , Sancho-Serra Carmen , Oszlanczi Agnes , Mazzeo Cecilia Icoresi , Hoffman Sophie , Krassowski Michał , Garbutt Kurtis , Kelava Iva , Gaitskell Kezia , Yancheva Slaveya , Woon Ee Von , Male Victoria , Granne Ingrid , Hellner Karin , Mahbubani Krishnaa T , Saeb-Parsy Kourosh , Lotfollahi Mohammad , Prigmore Elena , Southcombe Jennifer , Dragovic Rebecca A , Becker Christian M , Zondervan Krina T , Vento-Tormo Roser 
Published: November 2023

AbstractThe human endometrium, the inner lining of the uterus, exhibits complex, dynamic changes throughout the menstrual cycle in response to ovarian hormones. Aberrant response of endometrial cells to hormones is associated with multiple disorders, including endometriosis. Previous single-cell studies of the endometrium profiled a limited number of donors and lacked consensus in defining cell types and states. Here, we introduce the Human Endometrial Cell Atlas (HECA), a high-resolution single-cell reference atlas, combining published and newly generated single-cell transcriptomics datasets of endometrial biopsies of women with and without endometriosis. The HECA assigned consensus cell types and states, and uncovered novel ones, which we mapped in situ using spatial transcriptomics. We quantified how coordinated interactions between cell states in space and time contribute to endometrial regeneration and differentiation. In the continuously changingfunctionalislayer, we identified an intricate coordination of TGFβ signalling between stromal and epithelial cells, likely crucial for cell differentiation. In thebasalislayer, we defined signalling between fibroblasts and a new epithelial cell population expressing epithelial stem/progenitor markers, suggesting their role in endometrial regeneration. Additionally, integrating the HECA single-cell data with genome-wide association study data and comparing endometrial samples from women with and without endometriosis, we pinpointed subsets of decidualised stromal cells and macrophages as the most dysregulated cell states in endometriosis. Overall, the HECA is an invaluable resource for studying endometrial physiology, investigating endometrial disorders, and guiding the creation of endometrial microphysiologicalin vitrosystems.
Target-agnostic identification of human antibodies toPlasmodium falciparumsexual forms reveals cross stage recognition of glutamate-rich repeats
Authors: Amen Axelle , Yoo Randy , Fabra-García Amanda , Bolscher Judith , Stone William J.R. , Bally Isabelle , Dergan-Dylon Sebastián , Kucharska Iga , de Jong Roos M. , de Bruijni Marloes , Bousema Teun , Richter King C. , MacGill Randall S. , Sauerwein Robert W. , Julien Jean-Philippe , Poignard Pascal , Jore Matthijs M. 
Published: November 2023

AbstractCirculating sexual stages ofPlasmodium falciparum (Pf)can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies (Abs) can efficiently block parasite transmission. In search for naturally acquired Ab targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages ofPfin the form of gamete and gametocyte extract. We isolated mAbs reactive against a range ofPfproteins including well-established targets Pfs48/45 and Pfs230. One mAb, B1E11K, was cross-reactive to various proteins containing glutamate-rich repetitive elements expressed at different stages of the parasite life cycle. A crystal structure of two B1E11K Fab domains in complex with its main antigen, RESA, expressed on asexual blood stages, showed binding of B1E11K to a repeating epitope motif in a head-to-head conformation engaging in affinity-matured homotypic interactions. Thus, this mode of recognition ofPfproteins, previously described only for PfCSP, extends to other repeats expressed across various stages. The findings augment our understanding of immune-pathogen interactions to repeating elements of thePlasmodiumparasite proteome and underscore the potential of the novel mAb identification method used to provide new insights into the natural humoral immune response againstPf.Impact StatementA naturally acquired human monoclonal antibody recognizes proteins expressed at different stages of thePlasmodium falciparumlifecycle through affinity-matured homotypic interactions with glutamate-rich repeats
Pan-sphingolipid profiling reveals differential functions of sphingolipid biosynthesis isozymes ofC. elegans
Authors: Luo Hui , Zhao Xue , Wang Zi-Dan , Wu Gang , Xia Yu , Dong Meng-Qiu , Ma Yan 
Published: November 2023

AbstractMultiple isozymes are encoded in theC. elegansgenome for the various sphingolipid biosynthesis reactions, but the contributions of individual isozymes are characterized only in part. We developed a simple but effective reversed-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) method that enables simultaneous identification and quantification of ceramides (Cer), glucosylceramides (GlcCer), and sphingomyelins (SM), three important classes of sphingolipids from the same MS run. Validating this pan-sphingolipid profiling method, we show that nearly all 47 quantifiable sphingolipid species found in young adult worms were reduced upon RNA interference (RNAi) ofsptl-1orelo-5, which are required for synthesis of the id17:1 sphingoid base. We also confirm that HYL-1 and HYL-2, but not LAGR-1, constitute the major ceramide synthase activity with different preference for fatty acid substrates, and that CGT-3 plays a greater role than CGT-1 does in producing glucosylceramides. Intriguingly,lagr-1RNAi lowers the abundance of all sphingomyelin species and that of several glucosylceramide species, which suggests that LAGR-1 may have functions beyond what is predicted. Additionally, RNAi ofsms-1, −2,and-3all lower the abundance of sphingomyelins with an odd number of carbon atoms (mostly C21 and C23, with or without hydroxylation) in the N-acyl chain, and onlysms-1RNAi does not elevate sphingomyelins containing even-numbered N-acyl chains. This suggests that sphingolipids containing even-numbered N-acyl chains could be regulated separately, sometimes in opposite directions, with those containing odd-numbered N-acyls, presumably monomethyl branched chain fatty acyls. We also find that ceramide levels are kept in balance with those of glucosylceramides and sphingomyelins.
Geographic patterns of living tetrapod diversity reveal the signature of global diversification dynamics
Authors: Tejero-Cicuéndez Héctor , Menéndez Iris , Steell Elizabeth M. , Navalón Guillermo , Blanco Fernando , Šmíd Jiří 
Published: November 2023

AbstractBiodiversity is distributed unevenly among lineages and regions, and understanding the processes generating these global patterns is a central goal in evolutionary research, particularly in light of the current biodiversity crisis. Here, we integrate phylogenetic relatedness with species diversity patterns in four major clades of living tetrapods (amphibians, squamates, birds and mammals) to approach this challenge. We studied geographic patterns of richness-corrected phylogenetic diversity (residual PD), identifying regions where species are phylogenetically more closely or distantly related than expected by richness. We explored the effect of different factors in residual PD: recent speciation rates, temporal trends of lineage accumulation, and environmental variables. Specifically, we searched for evolutionary and ecological differences between regions of high and low residual PD. Our results reveal a nuanced relationship between recent speciation rates and residual PD, underscoring the role of recent speciation events in structuring current biogeographic patterns. Furthermore, we found differences between endothermic and ectothermic tetrapods in response to temperature and precipitation, highlighting the pivotal role of thermal physiology in shaping diversity dynamics. By illuminating the multifaceted factors underpinning global diversity patterns, our study represents a significant advancement towards more effective and holistic conservation approaches that are crucial to facing ongoing environmental challenges.
The evolutionary conserved choroid plexus sustains the homeostasis of brain ventricles in zebrafish
Authors: Jeong Inyoung , Andreassen Søren N. , Hoang Linh , Poulain Morgane , Seo Yongbo , Park Hae-Chul , Fürthauer Maximilian , MacAulay Nanna , Jurisch-Yaksi Nathalie 
Published: November 2023

SummaryThe choroid plexus produces cerebrospinal fluid (CSF) by transport of electrolytes and water from the vasculature to the brain ventricles. The choroid plexus plays additional roles in brain development and homeostasis by secreting neurotrophic molecules, and by serving as a CSF-blood barrier and immune interface. Prior studies have identified transporters on the epithelial cells that transport water and ions into the ventricles and tight junctions involved in the CSF-blood barrier. Yet, how the choroid plexus epithelial cells maintain the brain ventricle system and control brain physiology remain unresolved. To provide novel insights into the physiological roles of the choroid plexus, we use juvenile and adult zebrafish as model systems. Upon histological and transcriptomic analyses, we first identified that the zebrafish choroid plexus is highly conserved with the mammalian choroid plexus and that it expresses all transporters necessary for CSF secretion. Using novel genetic lines, we also identified that the choroid plexus secretes proteins into the CSF. Next, we generated a transgenic line allowing us to ablate specifically the epithelial cells in the choroid plexus. Using the ablation system, we identified a reduction of the ventricular sizes, but no alterations of the CSF-blood barrier. Altogether, our findings identified that the zebrafish choroid plexus is evolutionarily conserved and critical for maintaining the size and homeostasis of the brain ventricles.Graphical abstractHighlightsThe zebrafish choroid plexus has similar anatomical features with the mammalian choroid plexus.The expression of choroid plexus transporters involved in CSF secretion is evolutionarily conserved across vertebrates.Generation of a novel choroid plexus specific driver line shows that the choroid plexus epithelial cells secrete proteins into CSF.Ablation of the choroid plexus decreases the size of the brain ventricles.
DNA Origami Vesicle Sensors with Triggered Cargo Transfer
Authors: Büber Ece , Yaadav Renukka , Schröder Tim , Franquelim Henri G. , Tinnefeld Philip 
Published: November 2023

ABSTRACTInteracting with living systems typically involves the ability to address lipid membranes of cellular systems. The first step of interaction of a nanorobot with a cell will thus be the detection of binding to a lipid membrane. Leveraging the programmable nature of DNA origami, we engineered a biosensor harnessing single-molecule Fluorescence Resonance Energy Transfer (smFRET) as transduction mechanism for precise lipid vesicle detection. The system hinges on a hydrophobic ATTO647N modified single-stranded DNA (ssDNA) leash, protruding from a rectangular DNA origami. In a vesicle-free environment, the ssDNA adopts a coiled stance, ensuring high FRET efficiency. However, upon lipid vesicle binding to cholesterol anchors on the DNA origami, the hydrophobic ATTO647N induces the ssDNA to stretch towards the lipid bilayer, leading to reduced FRET efficiency. The strategic placement of cholesterol anchors further modulates this interaction, affecting the observed FRET populations. Beyond its role as a vesicle sensor, we show targeted cargo transport of the acceptor dye unit to the vesicle. The cargo transport is initiated by vesicle bound DNA and a strand displacement reaction. Our interaction platform opens pathways for innovative interaction such as biosensing and molecular transport with complex biosystems.
Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus
Authors: Rasetto Natalí B. , Giacomini Damiana , Berardino Ariel A. , Waichman Tomás Vega , Beckel Maximiliano S. , Di Bella Daniela J. , Brown Juliana , Davies-Sala M. Georgina , Gerhardinger Chiara , Lie Dieter Chichung , Arlotta Paola , Chernomoretz Ariel , Schinder Alejandro F. 
Published: November 2023

ABSTRACTThe adult hippocampus generates new granule cells (aGCs) that exhibit distinct functional capabilities along development, conveying a unique form of plasticity to the preexisting circuits. While early differentiation of adult radial glia-like neural stem cells (RGL) has been studied extensively, the molecular mechanisms guiding the maturation of postmitotic neurons remain unknown. Here, we used a precise birthdating strategy to follow newborn aGCs along differentiation using single-nuclei RNA sequencing (snRNA-seq). Transcriptional profiling revealed a continuous trajectory from RGLs to mature aGCs, with multiple sequential immature stages bearing increasing levels of effector genes supporting growth, excitability and synaptogenesis. Remarkably, four discrete cellular states were defined by the expression of distinct sets of transcription factors (TFs): quiescent neural stem cells, proliferative progenitors, postmitotic immature aGCs, and mature aGCs. The transition from immature to mature aCGs involved a transcriptional switch that shutdown molecular cascades promoting cell growth, such as the SoxC family of TFs, to activate programs controlling neuronal homeostasis. Indeed, aGCs overexpressingSox4orSox11remained stalled at the immature state. Our results unveil precise molecular mechanisms driving adult neural stem cells through the pathway of neuronal differentiation.
Lactate accumulation induced genioglossus myoblast injury under hypoxia
Authors: Zhang Menghan 
Published: November 2023

AbstractObstructive sleep apnea (OSA) is an increasingly common disorder of repeated upper airway collapse during sleep, leading to chronic intermittent hypoxia and metabolic alteration such as lactate accumulation. Genioglossus (GG), the largest upper airway dilator, is of great significance in maintaining the patency of the upper airway collapse. However, the lactate mechanism in OSA/CIH models is incomplete understood. Here, extracellular and intracellular contents of lactate were detected, and found hypoxia induced lactate accumulation in GG myoblasts. The we treat GG with lactate, and found lactate inhibited myoblasts proliferation and myotubes formation under hypoxia. When the lactate efflux was blocked by monocarboxylic acid transporter 1 (MCT1, a lactate transport) inhibitor AZD3965 (AZD), the expression levels of myogenic markers MyoD, Myogenin and MyHC were reduced. In summary, lactate efflux obstruction and lactate accumulation induced GG myoblast injury under hypoxia. These findings provide a theoretical basis for regulation lactate metabolism to alleviate muscle fatigue in the treatment of OSA.
SWISH-X, an expanded approach to detect cryptic pockets in proteins and at protein-protein interfaces
Authors: Borsatto Alberto , Gianquinto Eleonora , Rizzi Valerio , Gervasio Francesco Luigi 
Published: November 2023

AbstractProtein-protein interactions mediate most molecular processes in the cell, offering a significant opportunity to expand the set of known druggable targets. Unfortunately, targeting these interactions can be challenging due to their typically flat and featureless interaction surfaces, which often change as the complex forms. Such surface changes may reveal hidden (cryptic) druggable pockets. Here, we analyse a set of well-characterised protein-protein interactions harbouring cryptic pockets and investigate the predictive power of current computational methods. Based on our observations, we develop a new computational strategy, SWISH-X (SWISH Expanded), which combines the established cryptic pocket identification capabilities of SWISH with the rapid temperature range exploration of OPES MultiThermal. SWISH-X is able to reliably identify cryptic pockets at protein-protein interfaces while retaining its predictive power for revealing cryptic pockets in isolated proteins, such as TEM-1β-lactamase.