bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome
Authors: Amado Nathalia G. , Nosyreva Elena D. , Thompson David , Egeland Thomas J. , Ogujiofor Osita W. , Yang Michelle , Fusco Alexandria N. , Passoni Niccolo , Mathews Jeremy , Cantarel Brandi , Baker Linda A. , Syeda Ruhma 
Published: January 2024

AbstractPrune belly syndrome (PBS), also known as Eagle-Barret syndrome, is a rare, multi-system congenital myopathy primarily affecting males. Phenotypically, PBS cases manifest three cardinal pathological features: urinary tract dilation with poorly contractile smooth muscle, wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, and intra-abdominal undescended testes. Genetically, PBS is poorly understood. After performing whole exome sequencing in PBS patients, we identify one compound heterozygous variant in the PIEZO1 gene. PIEZO1 is a cation-selective channel activated by various mechanical forces and widely expressed throughout the lower urinary tract. Here we conduct an extensive functional analysis of the PIEZO1 PBS variants that reveal loss-of-function characteristics in the pressure-induced normalized open probability (NPo) of the channel, while no change is observed in single-channel currents. Furthermore, Yoda1, a PIEZO1 activator, can rescue the NPo defect of the PBS mutant channels. Thus, PIEZO1 mutations may be causal for PBS and the in vitro cellular pathophysiological phenotype could be rescued by the small molecule, Yoda1. Activation of PIEZO1 might provide a promising means of treating PBS and other related bladder dysfunctional states.
Functional host-specific adaptation of the intestinal microbiome in hominids
Authors: Rühlemann M. C. , Bang C. , Gogarten J. F. , Hermes B. M. , Groussin M. , Waschina S. , Poyet M. , Ulrich M. , Akoua-Koffi C. , Deschner T. , Muyembe-Tamfum J. J. , Robbins M. M. , Surbeck M. , Wittig R. M. , Zuberbühler K. , Baines J. F. , Leendertz F. H. , Franke A. 
Published: January 2024

AbstractFine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we perform high-resolution metagenomic-based analyzes of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in human populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny between microbes and hosts are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids. We find that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.
A uniform data processing pipeline enables harmonized nanoparticle protein corona analysis across proteomics core facilities
Authors: Gharibi Hassan , Ashkarran Ali Akbar , Jafari Maryam , Voke Elizabeth , Landry Markita P. , Saei Amir Ata , Mahmoudi Morteza 
Published: January 2024

AbstractProtein corona, a layer of biomolecules primarily comprising proteins, forms dynamically on nanoparticles in biological fluids and is crucial for predicting nanomedicine safety and efficacy. The protein composition of the corona layer is typically analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Our recent study, involving identical samples analyzed by 17 proteomics facilities, highlighted significant data variability, with only 1.8% of proteins consistently identified across these centers. Here, we implement an aggregated database search unifying parameters such as variable modifications, enzyme specificity, number of allowed missed cleavages and a stringent 1% false discovery rate at the protein and peptide levels. Such uniform search dramatically harmonizes the proteomics data, increasing the reproducibility and the percentage of consistency-identified unique proteins across distinct cores. Specifically, out of the 717 quantified proteins, 253 (35.3%) are shared among the top 5 facilities (and 16.2% among top 11 facilities). Furthermore, we note that reduction and alkylation are important steps in protein corona sample processing and as expected, omitting these steps reduces the number of total quantified peptides by around 20%. These findings underscore the need for standardized procedures in protein corona analysis, which is vital for advancing clinical applications of nanoscale biotechnologies.
Dietary emulsifier consumption accelerates type 1 diabetes development in NOD mice
Authors: Delaroque Clara , Chassaing Benoit 
Published: January 2024

AbstractThe rapidly increasing prevalence of type 1 diabetes (T1D) underscores the role of environmental (i.e. non-genetic) determinants of T1D development. Such factors include industrialized diets as well as the intestinal microbiota with which they interact. One component of industrialized diets that deleteriously impact gut microbiota is dietary emulsifiers, which perturb intestinal microbiota to encroach upon their host promoting chronic low-grade intestinal inflammation and metabolic syndrome. Hence, we investigated whether 2 dietary emulsifiers, carboxymethylcellulose (CMC) and polysorbate-80 (P80), might influence the development of T1D in NOD mice, which spontaneously develop this disorder. We observed that chronic emulsifier exposure accelerated T1D development in NOD mice, which was associated with increased insulin autoantibody levels. Such accelerated T1D development was accompanied by compositional and functional alterations of the intestinal microbiota as well as low-grade intestinal inflammation. Moreover, machine learning found that the severity of emulsifier-induced microbiota disruption had partial power to predict subsequent disease development, suggesting that complex interactions occur between the host, dietary factors, and the intestinal microbiota. Thus, perturbation of host–microbiota homeostasis by dietary emulsifiers may have contributed to the post-mid-20th-century increase in T1D.
Loss of the extracellular matrix glycoprotein EMILIN1 accelerates Δ16HER2-driven breast cancer initiation in mice
Authors: Favero Andrea , Segatto Ilenia , Capuano Alessandra , Mattevi Maria Chiara , Rampioni Vinciguerra Gian Luca , Musco Lorena , D’Andrea Sara , Dall’Acqua Alessandra , Gava Chiara , Perin Tiziana , Massarut Samuele , Marchini Cristina , Baldassarre Gustavo , Spessotto Paola , Belletti Barbara 
Published: January 2024

AbstractThe extracellular matrix (ECM) is an important component of the tumor microenvironment and undergoes extensive remodeling during both initiation and progression of breast cancer (BC). EMILIN1 is an ECM glycoprotein, whose function has been linked to cancer and metastasis. However, EMILIN1 role during mammary gland and BC development has never been investigated. In silico and molecular analyses of human samples from normal mammary gland and BC showed that EMILIN1 expression was lower in tumors than in healthy mammary tissue and it predicted poor prognosis, particularly in HER2-positive BC. HER2+ BC accounts for 15-20% of all invasive BC and is characterized by high aggressiveness and poor prognosis. The Δ16HER2 isoform, a splice variant with very high oncogenic potential, is frequently expressed in HER2+ BC and correlates with metastatic disease. To elucidate the role of EMILIN1 in BC, we analyzed the phenotype of MMTV-Δ16HER2 transgenic mice, developing spontaneous multifocal mammary adenocarcinomas, crossed with EMILIN1 knock-out (KO) animals. We observed that Δ16HER2/EMILIN1 KO female mice exhibited an accelerated normal mammary gland development and a significantly anticipated appearance of palpable tumors (13.32 vs 15.28 weeks). This accelerated tumor initiation was corroborated by an increased number of tumor foci observed in mammary glands from Δ16HER2/EMILIN1 KO mice compared to the wild-type counterpart. Altogether our results underscore the centrality of ECM in the process of BC initiation and point to a role for EMILIN1 during normal mammary gland development and in protecting from HER2-driven breast tumorigenesis.
Influence of Cr(III) on the formation and transformation of corrosion products of steel in marine environments
Authors: Serjaouan M. , Rémazeilles C. , Refait Ph. 
Published: January 2024

AbstractA fundamental approach is used to better understand the influence of Cr on the resistance of low alloy steel to marine corrosion. It focuses on the formation and transformation of corrosion products of steel in seawater-like electrolytes. Fe(OH)2 precipitates are then prepared by mixing a solution of NaCl, Na2SO4·10H2O, FeCl2·4H2O or FeCl2·4H2O + CrCl3·6H2O (so that Cr = 8% and Fe = 92%), with a solution of NaOH. The initial concentration ratio of reactants, $$Q=\frac{2[{{{\rm{Fe}}}}^{2+}]+3[{{{\rm{Cr}}}}^{3+}]}{[{{{\rm{OH}}}}^{-}]}$$

Q
=

2

[

Fe

2
+

]

+
3

[

Cr

3
+

]

[

OH

−

]

, is set at Q = 0.88, 1, and 1.136. In a first approach, the obtained aqueous suspension is stirred, at a controlled temperature of 25 ± 0.5 °C, to be oxidized by air. The resulting oxidation product is characterized by XRD and Raman spectroscopy. In a second approach, the Fe(OH)2 precipitates are aged one week in suspension in anoxic conditions, filtered, mixed as a wet paste with glycerol and set as a thin compact layer on the sample holder of a X-ray diffraction system. The oxidation process of Fe(OH)2 is then monitored in situ during the acquisition of the X-ray diffractogram. The obtained results demonstrate that Cr(III) hinders the formation of green rust compounds, hence hindering the formation of γ-FeOOH, i.e., the main oxidation product of green rust compounds. The other oxidation pathways of Fe(OH)2, which lead to Fe3O4 or α-FeOOH, are thus favored. Nevertheless, Cr(III) favors mainly the solid state transformation pathway of Fe(OH)2, thus promoting α-FeOOH via the formation of poorly ordered Fe(III) oxyhydroxides, namely feroxyhyte and ferrihydrite.
Unveiling multipole physics and frustration of icosahedral magnetic quasicrystals
Authors: Jeon Junmo , Lee SungBin 
Published: January 2024

AbstractMultipolar physics and their hidden orders have been widely discussed in the context of heavy fermions and frustrated magnets. However, despite extensive research, there are few examples of purely multipolar systems in the absence of magnetic dipoles. Here, we show the magnetic behavior of an icosahedral quasicrystal is generally described by multipoles, and in a specific case by pure magnetic octupoles, resulting from the interplay of spin-orbit coupling and crystal field splitting. Importantly, we emphasize that non-crystallographic symmetries of quasicrystals result in multipolar degrees of freedom, in contrast to the conventional crystals. We first classify the characteristics of multipoles and derive the effective spin Hamiltonian. We then explore how frustration and quantum fluctuations induce entangled quantum phases. Our study presents the magnetic icosahedral quasicrystal as a platform for investigating the exotic multipolar physics.
PvDBPII elicits multiple antibody-mediated mechanisms that reduce growth in a Plasmodium vivax challenge trial
Authors: Martinez Francisco J. , White Michael , Guillotte-Blisnick Micheline , Huon Christèle , Boucharlat Alix , Agou Fabrice , England Patrick , Popovici Jean , Hou Mimi M. , Silk Sarah E. , Barrett Jordan R. , Nielsen Carolyn M. , Reimer Jenny M. , Mukherjee Paushali , Chauhan Virander S. , Minassian Angela M. , Draper Simon J. , Chitnis Chetan E. 
Published: January 2024

AbstractThe receptor-binding domain, region II, of the Plasmodium vivax Duffy binding protein (PvDBPII) binds the Duffy antigen on the reticulocyte surface to mediate invasion. A heterologous vaccine challenge trial recently showed that a delayed dosing regimen with recombinant PvDBPII SalI variant formulated with adjuvant Matrix-MTM reduced the in vivo parasite multiplication rate (PMR) in immunized volunteers challenged with the Thai P. vivax isolate PvW1. Here, we describe extensive analysis of the polyfunctional antibody responses elicited by PvDBPII immunization and identify immune correlates for PMR reduction. A classification algorithm identified antibody features that significantly contribute to PMR reduction. These included antibody titre, receptor-binding inhibitory titre, dissociation constant of the PvDBPII-antibody interaction, complement C1q and Fc gamma receptor binding and specific IgG subclasses. These data suggest that multiple immune mechanisms elicited by PvDBPII immunization are likely to be associated with protection and the immune correlates identified could guide the development of an effective vaccine for P. vivax malaria. Importantly, all the polyfunctional antibody features that correlated with protection cross-reacted with both PvDBPII SalI and PvW1 variants, suggesting that immunization with PvDBPII should protect against diverse P. vivax isolates.
Gene modelling and annotation for the Hawaiian bobtail squid, Euprymna scolopes
Authors: Rogers Thea F. , Yalçın Gözde , Briseno John , Vijayan Nidhi , Nyholm Spencer V. , Simakov Oleg 
Published: January 2024

AbstractColeoid cephalopods possess numerous complex, species-specific morphological and behavioural adaptations, e.g., a uniquely structured nervous system that is the largest among the invertebrates. The Hawaiian bobtail squid (Euprymna scolopes) is one of the most established cephalopod species. With its recent publication of the chromosomal-scale genome assembly and regulatory genomic data, it also emerges as a key model for cephalopod gene regulation and evolution. However, the latest genome assembly has been lacking a native gene model set. Our manuscript describes the generation of new long-read transcriptomic data and, made using this combined with a plethora of publicly available transcriptomic and protein sequence data, a new reference annotation for E. scolopes.
Experimental study on dynamic characteristics of tailings under different consolidation conditions
Authors: Du Changbo , Jiang Xinqi , Wang Laigui , Yi Fu , Niu Ben 
Published: January 2024

AbstractThe dynamic stability of tailing ponds depend largely on the dynamic characteristics of tailings sand. To explore the dynamic characteristics of tailings sand under different consolidation conditions, consolidated undrained triaxial tests under different dry densities, consolidation ratios and containing pressures, the dynamic shear stress, liquefaction stress ratio, dynamic strength index, dynamic pore water pressure, dynamic modulus, and damping ratio of tailings sand under different consolidation conditions were analyzed. The dynamic shear stress linearly changed with the number of failure vibrations. The liquefaction stress ratio increases with an increase in consolidation ratio, conforming to the quadratic polynomial of the origin. With an increase in failure vibration times, the dynamic internal friction angle decreases gradually. Under different failure vibration times, the dynamic internal friction angle increases with an increase in consolidation ratio and dry density. An exponential function model of dynamic pore pressure growth suitable for equal pressure and bias consolidation conditions is proposed, and the fitting effect is favorable. The dynamic shear modulus ratio decreases with an increase in dynamic shear strain; the damping ratio increases with an increase in dynamic shear strain. The research results can provide a theoretical reference for seismic liquefaction of tailings dams in high-intensity seismic areas.
Investigating clot-flow interactions by integrating intravital imaging with in silico modeling for analysis of flow, transport, and hemodynamic forces
Authors: Teeraratkul Chayut , Tomaiuolo Maurizio , Stalker Timothy J. , Mukherjee Debanjan 
Published: January 2024

AbstractAs a blood clot forms, grows, deforms, and embolizes following a vascular injury, local clot-flow interactions lead to a highly dynamic flow environment. The local flow influences transport of biochemical species relevant for clotting, and determines the forces on the clot that in turn lead to clot deformation and embolization. Despite this central role, quantitative characterization of this dynamic clot-flow interaction and flow environment in the clot neighborhood remains a major challenge. Here, we propose an approach that integrates dynamic intravital imaging with computer geometric modeling and computational flow and transport modeling to develop a unifiedin silicoframework to quantify the dynamic clot-flow interactions. We outline the development of the methodology referred to as Intravital Integrated In Silico Modeling or , and then demonstrate the method on a sample set of simulations comprising clot formation following laser injury in two mouse cremaster arteriole injury model data: one wild-type mouse case, and one diYF knockout mouse case. Simulation predictions are verified against experimental observations of transport of caged fluorescent Albumin (cAlb) in both models. Through these simulations, we illustrate how the methodology can provide insights into hemostatic processes, the role of flow and clot-flow interactions, and enable further investigations comparing and contrasting different biological model scenarios and parameter variations.
An innovative staged prosthetic lengthening reconstruction strategy for osteosarcoma-related leg discrepancy
Authors: Xu Hairong , Li Yuan , Yu Feng , Liu Weifeng , Hao Lin , Zhang Qing , Niu Xiaohui 
Published: January 2024

AbstractCorrection of leg length discrepancy (LLD) in skeletally mature patients with osteosarcoma was rarely reported and quite challenging. This study aimed to propose a treatment strategy of staged lengthening and reconstruction with a standard static prosthesis to address LLD and restore limb function. It also evaluated the effectiveness of the strategy in terms of leg lengthening, functional outcomes, and complications. The strategy for lengthening included three stages. In stage 1, the previous prosthesis was removed and an external fixator with a temporary rod-cement spacer was placed. In this stage, the external fixator was used to lengthen the limb to the appropriate length. In stage 2, the external fixator was removed and the old rod-cement spacer was replaced with a new one. In stage 3, the rod-cement spacer was removed and the standard static prosthesis was planted. Nine skeletally mature distal femoral osteosarcoma patients with unacceptable LLD were treated in our institution from 2019 to 2021. We performed a chart review on nine patients for the clinical and radiographic assessment of functional outcomes, LLD, and complications. The mean (range) leg lengthening was 7.3 cm (3.6–15.6). The mean (range) LLD of the lower limbs decreased from 7.6 cm (4.1–14.2) before the lengthening to 0.3 cm (− 0.3 to 2.1) at the final follow-up with statistical significance (P = 0.000). The mean (range) Musculoskeletal Tumor Society score improved from 30.3% (16.7%–53.3%) before the lengthening to 96.3% (86.7%–100%) at the final follow-up with statistical significance (P = 0.000). Three patients (33.3%) had a minor complication; none needed additional surgical intervention. In the short term, the current staged lengthening and reconstruction with standard static prosthesis provided satisfactory functional outcomes and LLD correction with few complications. The long-term effects of this method need further exploration.
Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein
Authors: Pérez-Massón Beatriz , Quintana-Pérez Yazmina , Tundidor Yaima , Pérez-Martínez Dayana , Castro-Martínez Camila , Pupo-Meriño Mario , Orosa Ivette , Relova-Hernández Ernesto , Villegas Rosmery , Guirola Osmany , Rojas Gertrudis 
Published: January 2024

AbstractSARS-CoV-2 receptor binding domain (RBD) mediates viral entry into human cells through its interaction with angiotensin converting enzyme 2 (ACE2). Most neutralizing antibodies elicited by infection or vaccination target this domain. Such a functional relevance, together with large RBD sequence variability arising during viral spreading, point to the need of exploring the complex landscape of interactions between RBD-derived variants, ACE2 and antibodies. The current work was aimed at developing a simple platform to do so. Biologically active and antigenic Wuhan-Hu-1 RBD, as well as mutated RBD variants found in nature, were successfully displayed on filamentous phages. Mutational scanning confirmed the global plasticity of the receptor binding motif within RBD, highlighted residues playing a critical role in receptor binding, and identified mutations strengthening the interaction. The ability of vaccine-induced antibodies to inhibit ACE2 binding of many mutated RBD variants, albeit at different extents, was shown. Amino acid replacements which could compromise such inhibitory potential were underscored. The expansion of our approach could be the starting point for a large-scale phage-based exploration of diversity within RBD of SARS-CoV-2 and related coronaviruses, useful to understand structure–function relationships, to engineer RBD proteins, and to anticipate changes to watch during viral evolution.