bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative physiological plasticity ofAgastache rugosa(Fisch. & C.A.Mey.) Kuntze reveals complex adaptation to light and nutrient gradients
Authors: Rosli Khairul Azree , Misran Azizah , Yazan Latifah Saiful , Megat Wahab Puteri Edaroyati 
Published: October 2024

AbstractWe investigated the physiological plasticity ofAgastache rugosa(Fisch. & C.A.Mey.) Kuntze, in response to different light and nutrient levels, demonstrating complex adaptive strategies. Through comprehensive analysis of leaf traits, photosynthetic parameters, and resource use efficiencies, we uncovered unexpected patterns in Rubisco dynamics and nutrient utilization, particularly in low- light conditions.A. rugosaexhibited subtle thermal regulation, maintaining relatively stable leaf temperatures across treatments through coordinated adjustments in morphology and gas exchange. Multivariate analyses showed distinct clustering of traits, underlining the integrated nature of plant responses to environmental heterogeneity. Leaf area increased under low-light conditions, while leaf mass area was higher in high-light environments, consistent with shade avoidance syndrome and leaf economics spectrum theory. Surprisingly, Rubisco concentration and use efficiency were generally increased under low light, suggesting a compensatory mechanism. Water use efficiency was higher in high-light conditions, but photosynthetic phosphorus and potassium use efficiencies displayed surprising increases under low light. The species exhibited tight coordination between CO2supply and demand, as evidenced by strong correlations between net photosynthesis, stomatal conductance, and carboxylation efficiency. Our findings suggest thatA. rugosaemploys a suite of physiological and morphological adjustments to optimize resource acquisition and utilization that contribute to its ecological success.HighlightThis study reveals complex adaptive strategies inA. rugosaunder varying light and nutrient levels, showing unexpected patterns in Rubisco dynamics and nutrient use efficiencies while maintaining subtle thermal regulation across environments.
Coordinated control of genome-nuclear lamina interactions by Topoisomerase 2B and Lamin B receptor
Authors: Manzo Stefano G , van Schaik Tom , de Haas Marcel , Breda Jeremie , Magnitov Mikhail , de Wit Elzo , Manjon Anna G , Medema Rene H , Buckle Adam J , Naughton Catherine , Gilbert Nick , van Steensel Bas 
Published: October 2024

AbstractLamina-associated domains (LADs) are megabase-sized genomic regions anchored to the nuclear lamina (NL). Factors controlling the interactions of the genome with the NL have largely remained elusive. Here, we identified DNA topoisomerase 2 beta (TOP2B) as a regulator of these interactions. TOP2B binds predominantly to inter-LAD (iLAD) chromatin and its depletion results in a partial loss of genomic partitioning between LADs and iLADs, suggesting that its activity might protect specific iLADs from interacting with the NL. TOP2B depletion affects LAD interactions with lamin B receptor (LBR) more than with lamins. LBR depletion phenocopies the effects of TOP2B depletion, despite the different positioning of the two proteins in the genome. This suggests a complementary mechanism for organising the genome at the NL. Indeed, co-depletion of TOP2B and LBR causes partial LAD/iLAD inversion, reflecting changes typical of oncogene-induced senescence. We propose that a coordinated axis controlled by TOP2B in iLADs and LBR in LADs maintains the partitioning of the genome between the NL and the nuclear interior.HighlightsLADs and iLADs differ in supercoiling stateTOP2B controls genome partitioning between nuclear lamina and nuclear interiorTOP2B depletion preferentially affects genome interactions with LBRSimilar impact of TOP2B depletion and LBR depletion on genome-NL interactionsCo-depletion of TOP2B and LBR recapitulates LAD reshaping typical of oncogene-induced senescence.
UBR-1 deficiency leads to ivermectin resistance inC. elegans
Authors: Li Yi , Gong Long , Wu Jing , Hung Wesley , Zhen Mei , Gao Shangbang 
Published: October 2024

AbstractResistance to anthelmintics, particularly the macrocyclic lactone ivermectin (IVM), presents a substantial global challenge for parasite control. We found that the functional loss of an evolutionarily conserved E3 ubiquitin ligase, UBR-1, leads to IVM resistance inCaenorhabditis elegans. Multiple IVM-inhibiting activities, including viability, body size, pharyngeal pumping, and locomotion, were significantly ameliorated in variousubr-1mutants. Interestingly, exogenous application of glutamate induces IVM resistance in wild-type animals. The sensitivity of all IVM-affected phenotypes ofubr-1is restored by eliminating proteins associated with glutamate metabolism or signaling: GOT-1, a transaminase that converts aspartate to glutamate, and EAT-4, a vesicular glutamate transporter. We demonstrated that IVM-targeted GluCls (glutamate-gated chloride channels) are downregulated and that the IVM-mediated inhibition of serotonin-activated pharynx Ca2+activity is diminished inubr-1. Additionally, enhancing glutamate uptake inubr-1mutants through ceftriaxone completely restored their IVM sensitivity. Therefore, UBR-1 deficiency-mediated aberrant glutamate signaling leads to ivermectin resistance inC. elegans.
Sustained exposure to multivalent antigen-decorated nanoparticles generates broad anti-coronavirus responses
Authors: Baillet Julie , Klich John H. , Ou Ben S. , Meany Emily L. , Yan Jerry , Bruun Theodora U. J. , Utz Ashley , Jons Carolyn K. , Lecommandoux Sebastien , Appel Eric A. 
Published: October 2024

SummaryThe threat of future coronavirus pandemics requires developing cost-effective vaccine technologies that provide broad and long-lasting protection against diverse circulating and emerging strains. Here we report a multivalent liposomal hydrogel depot vaccine technology comprising the receptor binding domain (RBD) of up to four relevant SARS and MERS coronavirus strains non-covalently displayed on the surface of the liposomes within the hydrogel structure. The multivalent presentation and sustained exposure of RBD antigens improved the potency, neutralizing activity, durability, and consistency of antibody responses across homologous and heterologous coronavirus strains in a naïve murine model. When administrated in animals previously exposed to the wild-type SARS-CoV-2 antigens, liposomal hydrogels elicited durable antibody responses against the homologous SARS and MERS strains for over 6 months and elicited neutralizing activity against the immune-evasive SARS-CoV-2 variant Omicron BA.4/BA.5. Overall, the tunable antigen-decorated liposomal hydrogel platform we report here generates robust and durable humoral responses across diverse coronaviruses, supporting global efforts to effectively respond to future viral outbreaks.Progress and PotentialRapidly mutating infectious diseases such as influenza, HIV, and COVID-19 pose serious threats to human health. Yet, most vaccines still do not mount durable protection against mutagenic viruses and fail to induce broad responses to protect against emergent strains. Materials approaches to vaccine design, such as employing sustained delivery approaches or decorating nanoparticle constructs with multiple antigens, have shown promise in improving the breadth and potency of vaccines. Yet, these approaches typically require cumbersome chemistries and have not been explored in pre-exposed populations over clinically relevant time scales. Here, we report the development of an injectable liposomal hydrogel depot technology capable of prolonged presentation of multiple coronavirus antigens non-covalently coordinated on the surface of the liposomes forming the hydrogel structure. These hydrogels improve the potency, durability and breadth of vaccine response and are easy to fabricate, enabling the rapid design of next generation vaccines that confer protection against rapidly evolving pandemics.
Function of the alternative electron transport chain in theCryptosporidium parvummitosome
Authors: Deng Silu , Sibley L. David 
Published: October 2024

AbstractCryptosporidium parvum and C. hominispossess a remanent mitochondrion called the mitosome, which lacks DNA, the tricarboxylic acid cycle, a conventional electron transport chain, and ATP synthesis. The mitosome retains ubiquinone and iron sulfur cluster biosynthesis pathways, both of which require protein import that relies on the membrane potential. It was previously proposed that the membrane potential is generated by electrons transferred through an alternative respiratory pathway coupled to a transhydrogenase (TH) that pumps hydrogens out of the mitosome. This pathway relies on an alternative oxidase (AOX) and type II NADH dehydrogenase (NDH2), which also exists in plants, some fungi, and several protozoan parasites. To examine this model, we determined the location and function of AOX and NDH2 inC. parvum. Surprisingly, we observed that NDH2 was localized to parasite surface membranes instead of the mitosome. Furthermore, a Δndh2knockout (KO) strain was readily obtained, indicating that this protein is not essential for parasite growth. Although, AOX exhibited a mitosome-like staining pattern, we readily obtained an Δaoxknockout strain, indicating that AOX is also dispensable for parasite growth. The growth of the Δaoxstrain was inhibited by the AOX inhibitors SHAM and 8-HQ to the same extent as wild type, indicating that AOX is not the target of these inhibitors inC. parvum. Collectively, our studies indicate that NDH2 and AOX are non-essential genes inC. parvum, necessitating an alternative mechanism for maintaining the mitosome membrane potential.ImportanceCryptosporidiosis is the leading cause of diarrhea in young children and immunocompromised individuals, particularly AIDS/HIV patients. The only FDA approved drug against cryptosporidiosis, nitazoxanide, has limited effectivity in immunocompromised patients and is not approved for usage in children under 1 year old. Genomic analysis and previous studies proposed an alternative respiration pathway involving alternative oxidase (AOX) and type II NAD(P)H dehydrogenase (NDH2), which are thought to generate the mitosome membrane potential inC. parvum. Additionally, AOX and NDH2 were nominated as potential drug targets, based on their absence in mammalian hosts and sensitivity of parasite growth to known inhibitors of AOX. However, our study demonstrated that NDH2 is not localized in mitosome, AOX non-essential for parasite growth, and knockout lines lacking this enzyme are equally sensitive to AOX inhibitors. These findings indicate that AOX and NDH2 are not ideal candidates for future drug development against cryptosporidiosis and force a re-evaluation for models of how the mitosome generate its membrane potential.
Epigenome profiling identifies H3K27me3 regulation of extra-cellular matrix composition in human corticogenesis
Authors: Ditzer Nora , Senoglu Ezgi , Schütze Theresa M. , Nikolaidi Aikaterina , Kolodziejczyk Annika , Sameith Katrin , Dietz Sevina , Derihaci Razvan P. , Birdir Cahit , Eugster Anne , Karl Mike O. , Dahl Andreas , Wimberger Pauline , Baenke Franziska , Peitzsch Claudia , Albert Mareike 
Published: October 2024

SummaryEpigenetic mechanisms regulate gene expression programs during neurogenesis, but the extent of epigenetic remodelling during human cortical development remains unknown. Here, we characterize the epigenetic landscape of the human developing neocortex by leveraging Epi-CyTOF, a mass cytometry-based approach for the simultaneous single cell analysis of more than 30 epigenetic marks. We identify H3K27me3, deposited by Polycomb Repressive Complex 2 (PRC2), as the modification with the strongest cell type-specific enrichment. Inhibition of PRC2 in human cortical organoids resulted in a shift of neural progenitor cell (NPC) proliferation towards differentiation. Cell type- specific profiling of H3K27me3 not only identified neuronal differentiation genes in the human neocortex, but also extra-cellular matrix (ECM) genes. PRC2 inhibition resulted in increased production of the proteoglycan Syndecan 1. Overall, this study comprehensively characterizes the epigenetic state of specific neural cell types and highlights a novel role for H3K27me3 in regulating the ECM composition in the human developing neocortex.
Synthetic cell-based tissues for bottom-up assembly of artificial lymphatic organs
Authors: Burgstaller Anna , Lopez Lopez Erick Angel , Staufer Oskar 
Published: October 2024

AbstractSynthetic cells have emerged as novel biomimetic materials for studying fundamental cellular functions and enabling new therapeutic approaches. However, replicating the structure and function of complete tissues as self-organized 3D collectives has remained challenging. Here, we engineer lymph node-mimicking 3D lymphatic bottom-up tissues (lymphBUTs) with mechanical adaptability, metabolic activity, and hierarchical microstructural organization based on individual synthetic cells. We demonstrate that primary human immune cells spontaneously infiltrate and functionally integrate into these synthetic lymph nodes to form living tissue hybrids. By tuning the lymphBUT micro-organization and metabolic activity, we induce theex vivoexpansion of therapeutic CD8+T cells with an IL-10+/IL-17+regulatory phenotype. Our study highlights the functional integration of living and non-living matter, advancing synthetic cell engineering toward 3D tissue structures.
A fucose-binding superlectin fromEnterobacter cloacaewith high Lewis and ABO blood group antigen specificity
Authors: Beshr Ghamdan , Sikandar Asfandyar , Gläser Julia , Fares Mario , Sommer Roman , Wagner Stefanie , Köhnke Jesko , Titz Alexander 
Published: October 2024

AbstractBacteria frequently employ carbohydrate-binding proteins, so-called lectins, to colonize and persist in a host. Thus, bacterial lectins are attractive targets for the development of new antiinfectives. To find new potential targets for antiinfectives against pathogenic bacteria, we searched for homologs ofPseudomonas aeruginosalectins and identified homologs of LecA inEnterobacterspecies. Here, we recombinantly produced and biophysically characterized a homolog that comprises one LecA domain and one additional novel protein domain. This protein was termedEnterobacter cloacaelectin A (EclA) and found to bind L-fucose. Glycan array analysis revealed a high specificity for the LewisA antigen and the type II H-antigen (blood group O) for EclA, while related antigens LewisX, Y, and B as well as blood group A or B were not bound. We developed a competitive binding assay to quantify blood group antigen binding specificity in solution. Finally, the crystal structure of EclA could be solved in complex with methyl α-L-selenofucoside. It revealed the unexpected binding of the carbohydrate ligand to the second domain, which comprises a novel fold that dimerizes via strand-swapping resulting in an intertwined beta sheet.
Arthropod Diversity at Two Sites with Different Disturbance Levels at the Texas A&M International University
Authors: Siller Eduardo 
Published: October 2024

AbstractThis research aimed to measure arthropod species richness in two different sites with different disturbance levels in the Texas A&M International University campus to determine the overall biological diversity of the two sites and compare these measurements. As part of the research and methods, the Paleontological Statistics (PAST) software was used to calculate statistical indices in ecology that can help determine the difference between East and South sites. Some indices employed were the Shannon’s Diversity Index or the Simpson’s Index of Diversity, the Bray-Curtis matrix, and the iNaturalist app. Results showed that the abundance of arthropods differed significantly from one site to the other, with the South site having a greater quantity, which was the site with less degradation created by humans. The site with the degraded ecosystem (East site) did not show a clear disadvantage regarding the diversity of arthropods. Thus, this article is relevant considering abundance and diversity to discover which is more important in each location. Finally, the study provides more insight into the arthropod community in the South Texas region, which can help with land and ecosystem management.
Trafficking and translation of mRNA in osteocyte dendrites
Authors: Mazur Courtney M. , Kotsalidis Parthena E. , Castro Andrade Christian D. , Wu Mingrui , Wang Xiao , Taliaferro J. Matthew , Wein Marc N. 
Published: October 2024

ABSTRACTOsteocyte dendrites extend great distances through canaliculi in bone supported by an extensive cytoskeletal network. The formation and maintenance of osteocyte dendrites is closely linked to bone health, yet the mechanisms regulating these processes are poorly understood. Here we tested the hypothesis that osteocytes transport mRNA to their dendrites for local translation as a mechanism of regulating the formation and maintenance of these subcellular structures. Using molecular and imaging approaches, we demonstrated that a subset of mRNAs are enriched in Ocy454 osteocyte-like cell dendrites. To understand how certain mRNAs are directed to dendrites, we performed a massively parallel reporter assay with 7115 oligonucleotide sequences designed from the 3’ untranslated regions of eight dendrite-enriched transcripts. We identified localization sequences within some 3’UTRs that were both sufficient and necessary for trafficking to osteocyte dendrites, indicating that localization directions are specifically encoded in enriched transcripts. Furthermore, we found that dendrites contain the elements necessary for local translation, and trafficked transcripts were engaged in active translation within dendrites. Together this work describes a molecular regulatory mechanism novel to osteocyte biology with many potential consequences for the spatiotemporal control of the cytoskeleton and dendrites.
Structure of the CABIT2 domain of THEMIS reveals a novel protein fold with an inserted SH3-like domain
Authors: Beyett Tyler S. , Yurtsever Zeynep , Schaeffner Ilse K. , Rana Jaimin K. , Robbie Lucy K. , Ortiz-Salazar Daniela , Eck Michael J. 
Published: October 2024

AbstractMaturation of thymocytes into T cells is critical for proper function of the adaptive immune system. During this developmental process, thymocytes undergo a highly-regulated selection process regulated by the signaling characteristics of the T cell receptor (TCR) pathway. Thymocyte-Expressed Molecule Involved in Selection (THEMIS) is an essential protein for T cell development. THEMIS regulates phosphatases downstream of the T cell receptor to ensure signaling thresholds are met during selection. Important features of THEMIS are its two uncharacterized CABIT (Cysteine-containing All-Beta In THEMIS) domains, which are intriguing because they have been proposed to participate in important protein-protein interactions (PPIs) that modulate immunological signals. Here, we report the 2.9 Å crystal structure of the THEMIS CABIT2 domain determined via heavy atom phasing. The structure revealed a novel protein domain fold comprised mainly of β-sheets with two distinct subdomains. This domain appears to have a different C-terminal boundary than predicted or found in previously used experimental constructs. Inclusion of the proline rich segment enables GRB2 to bind CABIT2. Isolated CABIT2 domain is unable to bind or modulate the function of SHP1 phosphatase. This structure will provide the foundation for future structure-function studies of CABIT domains and THEMIS.
Implementation challenges for an optimised surgery blueprint schedule in a children’s hospital: an exploratory qualitative study using the CFIR framework
Authors: Vos Kelly , van Essen Theresia , Ista Erwin , Staals Lonneke , Hinrichs-Krapels Saba 
Published: October 2024

ABSTRACTCapacity management and planning for operating theatres involves scheduling surgeries, preparing beds, and ensuring available workforce. Numerous mathematical models have been developed in the scientific literature to optimise these schedules to aid planning decisions, but such models are rarely assessed for applicability and implementation within a hospital’s existing planning system. We address this implementation research gap by identifying the barriers and facilitators for adopting a mathematically optimised surgery blueprint schedule within a children’s hospital, using the Consolidated Framework for Implementation Research (CFIR). Facilitators for implementation of the schedule included a strong motivation among staff to optimise schedules given resource constraints and work burdens, as well as positive reactions towards an objectively designed mathematical scheduling tool. Barriers for implementation included a resistance to change among some staff, and the need for more evidence about the new schedule’s benefits before implementation. We identified a strong culture of operational adjustments made to schedules, which is a challenge to any optimised and centralised scheduling tool. Overall, we found that CFIR was a helpful tool for identifying specific innovation adoption factors for a proposed surgery scheduling model.
Simultaneous inversion of four physical parameters of hydrate reservoir for high accuracy porosity estimation
Authors: Yan Yuning , Li Hongbing 
Published: October 2024

AbstractEstimation of the porosity of a hydrate reservoir is essential for its exploration and development. However, the estimation accuracy was usually less certain in most previous studies that simply assumed that there is a linear relationship between the porosity and single‐elastic wave velocities or other rock physical parameters, thus affecting the evaluation of the reserves. In the three‐phase Biot‐type equations that are fundamental to model a hydrate‐bearing reservoir, porosity, alongside hydrate saturation, mineral constituent proportions and hydrate–grain contact factor, is non‐linearly responded by density, compressional and shear wave velocities. To improve porosity estimation, we propose to invert simultaneously four‐parameter (porosity, hydrate saturation, mineral constituent proportions and hydrate–grain contact factor) using an iteratively nonlinear interior‐point optimization algorithm to solve a nonlinear objective function that is a summation of the squared misfits between the well log and three‐phase Biot‐type equation–modelled density, compressional and shear wave velocities. A test in Mount Elbert gas hydrate research well was conducted for the case of a gas hydrate stratigraphic test well where elastic wave velocities, density, porosity and mineral composition analysis data are available. The four‐parameter inversion yielded a lower root mean square error for porosity (0.0245) across the entire well‐logging section compared to previous estimations from the linear relationship, post‐stacked and pre‐stacked seismic traces as well as the pore‐filling effective medium theory model applied to other well cases. Additionally, the other three parameters demonstrated good agreement with well logs. Inversion tests conducted at three additional hydrate sites also produced accurate results. Consequently, the new method surpasses previous approaches in porosity estimation accuracy.