bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-associated growth control modifies leaf proximodistal symmetry and enables leaf shape diversification
Authors: Li Xin-Min , Jenke Hannah , Strauss Sören , Wang Yi , Bhatia Neha , Kierzkowski Daniel , Lymbouridou Rena , Huijser Peter , Smith Richard S. , Runions Adam , Tsiantis Miltos 
Published: April 2024

SUMMARYBiological shape diversity is often manifested in modulation of organ symmetry and modification of the patterned elaboration of repeated shape elements.1–5Whether and how these two aspects of shape determination are coordinately regulated is unclear.5–7Plant leaves provide an attractive system to investigate this problem, because they usually show asymmetries along their proximodistal axis, along which they can also produce repeated marginal outgrowths such as serrations or leaflets.1One case of leaf shape diversity is heteroblasty, where the leaf form in a single genotype is modified with progressive plant age.8–11InArabidopsis thaliana,a plant with simple leaves, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE9 (SPL9) controls heteroblasty by activatingCyclinD3expression, thereby sustaining proliferative growth and retarding differentiation in adult leaves.12However, the precise significance of SPL9 action for leaf symmetry and marginal patterning is unknown. By combining genetics, quantitative shape analyses, and time-lapse imaging, we show that, inA. thaliana, proximodistal symmetry of the leaf blade decreases in response to an age-dependentSPL9expression gradient, and that SPL9 action coordinately regulates the distribution and shape of marginal serrations and overall leaf form. Using comparative analyses, we demonstrate that heteroblastic growth reprogramming inCardamine hirsuta,a complex-leafed relative ofA. thaliana,also involves prolonging the duration of cell proliferation and delaying differentiation. We further provide evidence that SPL9 enables species-specific action of homeobox genes that promote leaf complexity. In conclusion, we identify an age-dependent layer of organ proximodistal growth regulation that modulates leaf symmetry and has enabled leaf shape diversification.In BriefAge-dependent regulation of proliferative growth and differentiation along the proximodistal axis of leaves modulates organ symmetry and marginal patterning in heteroblasty, and enabled the action of homeobox genes in complex leaf shape evolution.HighlightsAn age-dependent growth gradient underpins regulation ofA. thalianaleaf symmetrySPL9-mediated heteroblastic growth control potentiates leaf histogenic capacityA common growth framework underlies heteroblasty in complex and simple leavesSPL9 enables the action of homeobox genes that promote leaf complexity
Targeting the Atypical Chemokine Receptor 2 (ACKR2) improves the benefit of anti-PD-1 immunotherapy in melanoma
Authors: Noman Muhammad Zaeem , Szpakowska Martyna , Xiao Malina , Van Moer Kris , Ollert Markus , Berchem Guy , Chevigné Andy , Janji Bassam 
Published: April 2024

AbstractImmune checkpoint blockade (ICB) therapies, targeting PD-1 or PD-L1, have transformed cancer treatment, particularly for aggressive cancers. However, many patients fail to benefit from ICBs due to tumor characteristics, including a non-inflammatory tumor microenvironment (TME) that impedes immune cell infiltration. This study investigated the potential of targeting the Atypical Chemokine Receptor 2 (ACKR2), known for scavenging CXCR3-related chemokines crucial for lymphocyte recruitment to tumors. Genetic targeting of ACKR2 in melanoma cells increased the release of essential chemokines associated with the inflamed TME. In mouse models, ACKR2 inhibition suppressed tumor growth, improved survival, and enhanced activated immune cell infiltration into the TME. Moreover, ACKR2 targeting synergized with anti-PD-1 therapy, overcoming resistance to anti-PD-1 and improving its efficacy. Analysis of melanoma patient data from The Cancer Genome Atlas (TCGA) revealed that patients with high levels of chemokines scavenged by ACKR2 had significantly better survival rates, with increased expression of NK cell and CD8 T cell markers indicating their presence in the TME. Notably, even in patients with high CD8 expression, those expressing low ACKR2 survived better than those expressing high ACKR2. This study emphasizes the clinical importance of targeting ACKR2 as an attractive strategy for the development of combination immunotherapies to treat cold tumors, which are clinically stratified to not be eligible for ICB-based therapy.
Text-related functionality and dynamics of visual human pre-frontal activations revealed through neural network convergence
Authors: Shoham Adva , Broday-Dvir Rotem , Yaron Itay , Yovel Galit , Malach Rafael 
Published: April 2024

SummaryThe functional role of visual activations of human pre-frontal cortex remains a deeply debated question. Its significance extends to fundamental issues of functional localization and global theories of consciousness. Here we addressed this question by comparing, dynamically, the potential parallels between the relational structure of prefrontal visual activations and visual and textual-trained deep neural networks (DNNs). The frontal visual relational structures were revealed in intra-cranial recordings of human patients, conducted for clinical purposes, while the patients viewed familiar images of faces and places. Our results reveal that visual relational structures in frontal cortex were, surprisingly, predicted by text and not visual DNNs. Importantly, the temporal dynamics of these correlations showed striking differences, with a rapid decline over time for the visual component, but persistent dynamics including a significant image offset response for the text component. The results point to a dynamic text-related function of visual prefrontal responses in the human brain.
MPRAVarDB: an online database and web server for exploring regulatory effects of genetic variants
Authors: Nizomov Javlon , Jin Weijia , Xia Yi , Liu Yunlong , Li Zhigang , Chen Li 
Published: April 2024

AbstractSummaryMassively parallel reporter assay (MPRA) is an important technology to evaluate the impact of genetic variants on gene regulation. Here, we present MPRAVarDB, an online database and web server, for exploring regulatory effects of genetic variants. MPRAVarDB harbors 18 MPRA experiments designed to assess the regulatory effects of genetic variants associated with GWAS loci, eQTLs and various genomic features, resulting in a total of 242,818 variants tested across more than 30 cell lines and 30 human diseases or traits. MPRAVarDB empowers the query of MPRA variants by genomic region, disease and cell line or by any combination of these query terms. Notably, MPRAVarDB offers a suite of pretrained machine learning models tailored to the specific disease and cell line, facilitating the genome-wide prediction of regulatory variants. MPRAVarDB is friendly to use, and users only need a few clicks to receive query and prediction results.Availabilityhttps://mpravardb.rc.ufl.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
High-resolutionIn-situStructures of Mammalian Mitochondrial Respiratory Supercomplexes in Reaction within Native Mitochondria
Authors: Zheng Wan , Chai Pengxin , Zhu Jiapeng , Zhang Kai 
Published: April 2024

ABSTRACTMitochondria play a pivotal role in ATP energy production through oxidative phosphorylation, which occurs within the inner membrane via a series of respiratory complexes. Despite extensivein-vitrostructural studies, revealing the atomic details of their molecular mechanisms in physiological states remains a major challenge, primarily because of the loss of the native environment during purification. Here, we directly image porcine mitochondria using anin-situcryo-electron microscopy approach. This enables us to determine the structures of various high-order assemblies of respiratory supercomplexes in their native states, achieving up to 1.8-Å local resolution. We identify four major supercomplex organizations: I1III2IV1, I1III2IV2, I2III2IV2, and I2III4IV2, which can potentially expand into higher-order arrays on the inner membranes. The formation of these diverse supercomplexes is largely contributed by ‘protein-lipids-protein’ interactions, which in turn dramatically impact the local geometry of the surrounding membranes. Ourin-situstructures also capture numerous reactive intermediates within these respiratory supercomplexes, shedding light on the dynamic processes of the ubiquinone/ubiquinol exchange mechanism in complex I and the Q-cycle in complex III. By comparing supercomplex structures from mitochondria treated under distinct conditions, we elucidate how conformational changes and ligand binding states interplay between complexes I and III in response to environmental redox alterations. Our approach, by preserving the native membrane environment, enables structural studies of mitochondrial respiratory supercomplexes in reaction at high resolution across multiple scales, spanning from atomic-level details to the broader subcellular context.
Plant Growth analysis using computer. An auxiliary computational program. II
Authors: Portes Tomás de Aquino 
Published: April 2024

AbstractThe result of photosynthetic activity by plants is mass gain. Essential mineral elements are immobilized in the plant mass, the main element being carbon. In photosynthesis, this element is linked to one another forming carbon chains and to link one carbon to another the plant uses solar energy, making the mass rich in energy. Therefore, quantifying plant mass is interesting to estimate the efficiency of plants in accumulating mass and energy. Mass quantification is done using the growth analysis technique. The objective of this work was to develop a computer program to assist in the plant growth analysis. It consisted of adjusting mathematical equations to data on leaf area, total and leaf dry mass. Once the best equations were found, the instantaneous growth indicators, CGR, RGR, NAR, SLA, LAR, LAD and carbon flux (pn) were estimated from them. The adjusted equations were linear, logistic, quadratic, cubic, quadratic exponential and cubic exponential. The equations that best fit to the data were the quadratic exponential and cubic exponential. The program was developed in the C* language. For comparison purposes, the average physiological indicators of growth were estimated using the classic equations found in the literature.HighlightPlant growth analysis is a very useful technique for evaluating plant mass gain. To facilitate the analysis, a computer program presented in this article was developed. The software is important because there is nothing similar available and will facilitate the work of researchers working on the subject
GLP1R agonists activate human POMC neurons
Authors: Mazzaferro Simone , Chen Hsiao-Jou Cortina , Cahn Oliver , Yang Andrian , Shepilov Dmytro , Chen Jiahui , Alcaino Contanza , Macarelli Viviana , Mali Iman , Gribble Fiona , Reimann Frank , Marioni John , Merkle Florian T. 
Published: April 2024

AbstractDrugs like Semaglutide (a.k.a. Ozempic/Wegovy) that activate the glucagon-like peptide-1 receptor (GLP1R) are a promising therapy for obesity and type 2 diabetes (T2D). Animal studies suggest that appetite-suppressing proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus are a likely target of these drugs, but the mechanisms by which they reduce food intake in humans are still unclear. We therefore generated POMC neurons from human pluripotent stem cells (hPSCs) to study their acute responses to GLP1R agonists by calcium imaging and electrophysiology. We found that hPSC-derived POMC neurons expressedGLP1Rand many of them robustly responded to GLP1R agonists by membrane depolarization, increased action potential firing rate, and extracellular calcium influx that persisted long after agonist withdrawal and was likely mediated by L-type calcium channels. Prolonged administration of Semaglutide upregulated transcriptional pathways associated with cell survival in POMC neurons, and downregulated pathways associated with oxidative stress and neurodegeneration. These findings suggest that POMC neurons contribute to the long-term appetite-suppressive effects of GLP1R agonists in humans.
Leading researchers in the leadership of leading research universities: meta-research analysis
Authors: Ioannidis John 
Published: April 2024

ABSTRACTIt is unknown to what extent leading researchers are currently involved in the leadership of leading research universities as presidents or as executive board members. The academic administrative leader (president or equivalent role) of each of the 146 Carnegie tier 1 USA universities and of any of the top-100 universities per Times Higher Education (THE) 2024 ranking and the members of the executive governing bodies (Board of Trustees, Council, Corporation or similar) for the each of the top-20 universities per THE 2024 ranking were examined for high citation impact in their scientific subfield. Highly-cited was defined as the top-2% of a composite citation indicator (that considers citations, h-index, co-authorship adjusted hm-index and citations to papers as single, first, last authors) in their main scientific subfield based on career-long impact until end-2022 among all scholars focusing in the same subfield and having published ≥5 full papers. Very highly-cited was similarly defined as the top-0.2%. Science was divided into 174 fields per Science-Metrix classification. 38/146 (26%) tier 1 USA university leaders as of end-2023 were highly-cited and 5/146 (3%) were very highly-cited. The respective figures for the top-100 THE 2024 universities globally were 43/100 and 12/100. For the 13 US universities among the top-20 of THE 2024, the probability of their leader being highly-cited was lower (6/13, 46%) than the probability of a randomly chosen active full tenured professor from their faculty being highly-cited (52-77%). Across 444 board members of 14 top-10 THE 2024 universities with data, only 65 (15%) were academics, and 19 (4%) were highly-cited; academics were rare in USA university boards. Board members had predominantly careers in for-profit companies. In conclusion, leading research universities have a dearth of leaders who are high-impact researchers.
Cell-specific polymerization-driven biomolecular condensate formation fine-tunes root tissue morphogenesis
Authors: Su Jianbin , Xu Xianjin , Cseke Leland J. , Whittier Sean , Zhou Ruimei , Zhang Zhengzhi , Dietz Zackary , Singh Kamal , Yang Bing , Chen Shi-You , Picking William , Zou Xiaoqin , Gassmann Walter 
Published: April 2024

ABSTRACTFormation of biomolecular condensates can be driven by weak multivalent interactions and emergent polymerization. However, the mechanism of polymerization-mediated condensate formation is less studied. We found lateral root cap cell (LRC)-specific SUPPRESSOR OF RPS4-RLD1 (SRFR1) condensates fine-tune primary root development. Polymerization of the SRFR1 N-terminal domain is required for both LRC condensate formation and optimal root growth. Surprisingly, the first intrinsically disordered region (IDR1) of SRFR1 can be functionally substituted by a specific group of intrinsically disordered proteins known as dehydrins. This finding facilitated the identification of functional segments in the IDR1 of SRFR1, a generalizable strategy to decode unknown IDRs. With this functional information we further improved root growth by modifying the SRFR1 condensation module, providing a strategy to improve plant growth and resilience.
Genetic editing of primary human dorsal root ganglion neurons using CRISPR-Cas9 with functional confirmation
Authors: Palomino Seph , Gabriel Katherin , Mwirigi Juliet , Cervantes Anna , Horton Peter , Funk Geoffrey , Moutal Aubin , Martin Laurent , Khanna Rajesh , Price Theodore , Patwardhan Amol 
Published: April 2024

AbstractCRISPR-Cas9 editing is now the leading method for genome editing and is being advanced for the treatment of human disease. CRIPSR editing could have many applications for treatment of neurological diseases, including pain but traditional viral vector delivery approaches have neurotoxicity limiting their use. Overcoming these issues could open the door for genome editing treatments for diseases like intractable pain where the dorsal root ganglia (DRG) would be the desired target. To this end, we describe a simple method for viral-vector-independent transfection of primary human DRG (hDRG) neurons for CRISPR-Cas9 editing. As proof of principle, we editedTRPV1, NTSR2, andCACNA1Eusing a lipofection method with CRISPR-Cas9 plasmids containing reporter tags (GFP or mCherry). Transfection was successful as demonstrated by the expression of the reporters as early as two daysin vitro. CRISPR-Cas9 editing was confirmed at the genome level with insertion and deletion detection system T7-endonuclease-I assay; protein level with immunocytochemistry and Western blot; and functional level through capsaicin-induced Ca2+accumulation in a high-throughput compatible fluorescent imaging plate reader (FLIPR) system. This work establishes a reliable, target specific, non-viral CRISPR-Cas9-mediated genetic editing in primary human neurons with potential for future clinical application for intractable pain.TeaserWe describe a non-viral transfection method for CRISPR-Cas9 gene editing in human dorsal root ganglion neurons.
Native molecular architectures of centrosomes inC. elegansembryos
Authors: Tollervey Fergus , Rios Manolo U. , Zagoriy Evgenia , Woodruff Jeffrey B. , Mahamid Julia 
Published: April 2024

AbstractCentrosomes organize microtubules that are essential for mitotic divisions in animal cells. They consist of centrioles surrounded by Pericentriolar Material (PCM). Questions related to mechanisms of centriole assembly, PCM organization, and microtubule formation remain unanswered, in part due to limited availability of molecular-resolution structural analysesin situ. Here, we use cryo-electron tomography to visualize centrosomes across the cell cycle in cells isolated fromC. elegansembryos. We describe a pseudo-timeline of centriole assembly and identify distinct structural features including a cartwheel in daughter centrioles, and incomplete microtubule doublets surrounded by a star-shaped density in mother centrioles. We find that centriole and PCM microtubules differ in protofilament number (13 versus 11) indicating distinct nucleation mechanisms. This difference could be explained by atypical γ-tubulin ring complexes with 11-fold symmetry identified at the minus ends of short PCM microtubules. We further characterize a porous and disordered network that forms the interconnected PCM. Thus, our work builds a three-dimensional structural atlas that helps explain how centrosomes assemble, grow, and achieve function.
The kinesin motor Kif9 regulates centriolar satellite positioning and mitotic progression
Authors: Vicente Juan Jesus , Wagenbach Michael , Decarreau Justin , Zelter Alex , MacCoss Michael J. , Davis Trisha N. , Wordeman Linda 
Published: April 2024

SUMMARYCentrosomes are the principal microtubule-organizing centers of the cell and play an essential role in mitotic spindle function. Centrosome biogenesis is achieved by strict control of protein acquisition and phosphorylation prior to mitosis. Defects in this process promote fragmentation of pericentriolar material culminating in multipolar spindles and chromosome missegregation. Centriolar satellites, membrane-less aggrupations of proteins involved in the trafficking of proteins toward and away from the centrosome, are thought to contribute to centrosome biogenesis. Here we show that the microtubule plus-end directed kinesin motor Kif9 localizes to centriolar satellites and regulates their pericentrosomal localization during interphase. Lack of Kif9 leads to aggregation of satellites closer to the centrosome and increased centrosomal protein degradation that disrupts centrosome maturation and results in chromosome congression and segregation defects during mitosis. Our data reveal roles for Kif9 and centriolar satellites in the regulation of cellular proteostasis and mitosis.
Towards self-regeneration: exploring the limits of protein synthesis in the PURE cell-free transcription-translation system
Authors: Ganesh Ragunathan Bava , Maerkl Sebastian J. 
Published: April 2024

AbstractSelf-regeneration is a key function of living systems that needs to be recapitulatedin vitroto create a living synthetic cell. A major limiting factor for protein self-regeneration in the PURE cell-free transcription-translation system is its high protein concentration, which far exceed the system’s protein synthesis rate. Here we were able to drastically reduce the non-ribosomal PURE protein concentration up to 97.3% while increasing protein synthesis efficiency. Although crowding agents were not effective in the original PURE formulation, we found that in highly dilute PURE formulations addition of 6% dextran considerably increased protein synthesis rate and total protein yield. These new PURE formulations will be useful for many cell-free synthetic biology applications and we estimate that PURE can now support the complete self-regeneration of all 36 non-ribosomal proteins, which is a critical step towards the development of a universal biochemical constructor and living synthetic cell.
Rapid small-scale nanobody-assisted purification of ryanodine receptors for cryo-EM
Authors: Li Chenyao , Willegems Katrien , Uchański Tomasz , Pardon Els , Steyaert Jan , Efremov Rouslan G. 
Published: April 2024

AbstractRyanodine receptors (RyRs) are large Ca2+release channels residing in the endoplasmic or sarcoplasmic reticulum membrane. Three isoforms of RyRs were identified in mammals, disfunction of which was associated with a series of life-threatening diseases. Advances in structural studies of RyRs are limited by the need for large amounts of native tissue or eukaryotic cell cultures. Here, we report a method that utilizes nanobodies to purify RyRs from only 5 mg of total protein. The purification starting from isolated membranes to cryo-EM grade protein is completed within four hours on the bench and produces protein usable for cryo-EM as we show by solving the structures of rabbit RyR1 and bovine and mouse RyR2 solubilized in detergent, reconstituted into lipid nanodiscs or liposomes. The reported method facilitates structural studies of RyRs directed toward drug development and is useful in the cases where the amount of starting material is limited.
A novel method for estimation of electrode kinetics parameters
Authors: Wang Yongjing , Liu Yingwei 
Published: April 2024

Purpose
The purpose of this paper is to extract electrochemical reaction kinetics parameters, such as Tafel slope, exchange current density and equilibrium potential, which cannot be directly measured, this study aims to propose an improved particle swarm optimization (PSO) algorithm.

Design/methodology/approach
In traditional PSO algorithms, each particle’s historical optimal solution is compared with the global optimal solution in each iteration step, and the optimal solution is replaced with a certain probability to achieve the goal of jumping out of the local optimum. However, this will to some extent undermine the (true) optimal solution. In view of this, this study has improved the traditional algorithm: at each iteration of each particle, the historical optimal solution is not compared with the global optimal solution. Instead, after all particles have iterated, the optimal solution is selected and compared with the global optimal solution and then the optimal solution is replaced with a certain probability. This to some extent protects the global optimal solution.

Findings
The polarization curve plotted by this equation is in good agreement with the experimental values, which demonstrates the reliability of this algorithm and provides a new method for measuring electrochemical parameters.

Originality/value
This study has improved the traditional method, which has high accuracy and can provide great support for corrosion research.