bluuebunny/crossref_metadata_2025_split huggingface dataset:
ICAM2 initiates trans-blood-CSF barrier migration and stemness properties in leptomeningeal metastasis of triple-negative breast cancer
Authors: Pan Jhih-Kai , Lin Wen-Der , Kuo Yao-Lung , Chen Yu-Chia , Loh Zhu-Jun , Lin Forn-Chia , Cheng Hui-Chuan , Hsiao Michael , Lu Pei-Jung 
Published: August 2023

AbstractLeptomeningeal metastasis (LM) occurs when tumor cells spread to the leptomeningeal space surrounding the brain and the spinal cord, thereby causing poor clinical outcomes. The triple-negative breast cancer (TNBC) has been associated with symptoms of LM and mechanism remained unclear. Through proteomic analysis, we identified high expression of ICAM2 in leptomeningeal metastatic TNBC cells, which promoted the colonization of the spinal cord and resulted in poor survival in vivo. Two-way demonstration indicated that high levels of ICAM2 promoted blood–cerebrospinal fluid barrier (BCB) adhesion, trans-BCB migration, and stemness abilities and determined the specificity of LM in vivo. Furthermore, pull-down and antibody neutralizing assay revealed that ICAM2 determined the specificity of LM through interactions with ICAM1 in the choroid plexus epithelial cells. Therefore, neutralizing ICAM2 can attenuate the progression of LM and prolong survival in vivo. The results suggested that targeting ICAM2 is a potential therapeutic strategy for LM in TNBC.
Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5
Authors: Diegel Cassandra R. , Kramer Ina , Moes Charles , Foxa Gabrielle E. , McDonald Mitchell J. , Madaj Zachary B. , Guth Sabine , Liu Jun , Harris Jennifer L. , Kneissel Michaela , Williams Bart O. 
Published: August 2023

AbstractProper regulation of Wnt signaling is critical for normal bone development and homeostasis. Mutations in several Wnt signaling components, which increase the activity of the pathway in the skeleton, cause high bone mass in human subjects and mouse models. Increased bone mass is often accompanied by severe headaches from increased intracranial pressure, which can lead to fatality and loss of vision or hearing due to the entrapment of cranial nerves. In addition, progressive forehead bossing and mandibular overgrowth occur in almost all subjects. Treatments that would provide symptomatic relief in these subjects are limited. Porcupine-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled receptor. Chemical inhibition of porcupine is a highly selective method of Wnt signaling inhibition. We treated three different mouse models of high bone mass caused by aberrant Wnt signaling, including homozygosity for loss-of-function inSost, which models sclerosteosis, and two strains of mice carrying different point mutations inLrp5(equivalent to human G171V and A214V), at 3 months of age with porcupine inhibitors for 5–6 weeks. Treatment significantly reduced both trabecular and cortical bone mass in all three models. This demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.
FOXM1 maintains fatty acid homoeostasis through the SET7-H3K4me1-FASN axis
Authors: Li Xixi , Su Weijie , Wu Honglin , Xu Jiakun , Tang Hongxing , Chen Xiangkun , Yin Zhanqi , Zhang Changming , Yang Jia , Yang Yibing , Zhang Nu , Yang Lixuan 
Published: August 2023

AbstractReprogramming of metabolic genes and subsequent alterations in metabolic phenotypes occur widely in malignant tumours, including glioblastoma (GBM). FOXM1 is a potent transcription factor that plays an oncogenic role by regulating the expression of many genes. As a SET domain containing protein, SET7 is a protein lysine methyltransferase which monomethylates histone proteins and other proteins. The epigenetic modification of histones regulates gene expressions by epigenetically modifying promoters of DNAs and inter vening in tumor development. Activation of FASN increased de novo fatty acid (FA) synthesis, a hallmark of cancer cells. Here, we report that FOXM1 may directly promote the transcription of SET7 and activate SET7-H3K4me1-FASN axis, which results in the maintenance of de novo FA synthesis.
Citrullinated fibrinogen-SAAs complex causes vascular metastagenesis
Authors: Han Yibing , Tomita Takeshi , Kato Masayoshi , Ashihara Norihiro , Higuchi Yumiko , Matoba Hisanori , Wang Weiyi , Hayashi Hikaru , Itoh Yuji , Takahashi Satoshi , Kurita Hiroshi , Nakayama Jun , Okumura Nobuo , Hiratsuka Sachie 
Published: August 2023

AbstractPrimary tumor cells metastasize to a distant preferred organ. However, the most decisive host factors that determine the precise locations of metastases in cancer patients remain unknown. We have demonstrated that post-translational citrullination of fibrinogen creates a metastatic niche in the vulnerable spots. Pulmonary endothelial cells mediate the citrullination of fibrinogen, changing its conformation, surface charge, and binding properties with serum amyloid A proteins (SAAs), to make it a host tissue-derived metastatic pathogen. The human-specific SAAs-citrullinated fibrinogen (CitFbg) complex recruits cancer cells to form a protein-metastatic cell aggregation in humanized SAA cluster mice. Furthermore, a CitFbg peptide works as a competitive inhibitor to block the homing of metastatic cells into the SAAs-CitFbg sites. The potential metastatic sites in the lungs of patients are clearly visualized by our specific antibody for CitFbg. Thus, CitFbg deposition displays metastatic risks for cancer patients, and the citrullinated peptide is a new type of metastasis inhibitor.
Fiber supplementation protects from antibiotic-induced gut microbiome dysbiosis by modulating gut redox potential
Authors: Penumutchu Swathi , Korry Benjamin J. , Hewlett Katharine , Belenky Peter 
Published: August 2023

AbstractAntibiotic-induced gut dysbiosis (AID) is a frequent and serious side effect of antibiotic use and mitigating this dysbiosis is a critical therapeutic target. We propose that the host diet can modulate the chemical environment of the gut resulting in changes to the structure and function of the microbiome during antibiotic treatment. Gut dysbiosis is typically characterized by increases in aerobic respiratory bacterial metabolism, redox potential, and abundance of Proteobacteria. In this study, we explore dietary fiber supplements as potential modulators of the chemical environment in the gut to reduce this pattern of dysbiosis. Using defined-diets and whole-genome sequencing of female murine microbiomes during diet modulation and antibiotic treatment, we find that fiber prebiotics significantly reduced the impact of antibiotic treatment on microbiome composition and function. We observe reduced abundance of aerobic bacteria as well as metabolic pathways associated with oxidative metabolism. These metatranscriptomic results are corroborated by chemical measurements of eH and pH suggesting that fiber dampens the dysbiotic effects of antibiotics. This work indicates that fiber may act as a potential therapeutic for AID by modulating bacterial metabolism in the gut to prevent an increase in redox potential and protect commensal microbes during antibiotic treatment.
Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
Authors: Hiltbrunner Stefanie , Cords Lena , Kasser Sabrina , Freiberger Sandra N. , Kreutzer Susanne , Toussaint Nora C. , Grob Linda , Opitz Isabelle , Messerli Michael , Zoche Martin , Soltermann Alex , Rechsteiner Markus , van den Broek Maries , Bodenmiller Bernd , Curioni-Fontecedro Alessandra 
Published: August 2023

AbstractImmune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8+ T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC.
Divergent access to 5,6,7-perifused cycles
Authors: Han Jingpeng , Yang Yongjian , Gong Yingjian , Tang Xuan , Tian Yi , Li Baosheng 
Published: August 2023

AbstractNitrogen-containing heterocycles are the key components in many pharmaceuticals and functional materials. In this study, we report a transition metal-catalyzed high-order reaction sequence for synthesizing a structurally unique N-center 5,6,7-perifused cycle (NCPC). The key characteristics include the formation of a seven-membered ring by the 8π electrocyclization of various alkenes and aromatic heterocycles as π-components, in which metal carbene species are generated that further induce the cleavage of the α-C-H or -C-C bond. Specifically, the latter can react with various nucleophilic reagents containing -O, -S, -N, and -C. The stereo-controlled late-stage modification of some complicated pharmaceuticals indicates the versatility of this protocol.
Synthesis of robust underwater glues from common proteins via unfolding-aggregating strategy
Authors: Liu Yongchun , Li Ke , Tian Juanhua , Gao Aiting , Tian Lihua , Su Hao , Miao Shuting , Tao Fei , Ren Hao , Yang Qingmin , Cao Jing , Yang Peng 
Published: August 2023

AbstractUnderwater adhesive proteins secreted by organisms greatly inspires the development of underwater glue. However, except for specific proteins such as mussel adhesive protein, barnacle cement proteins, curli protein and their related recombinant proteins, it is believed that abundant common proteins cannot be converted into underwater glue. Here, we demonstrate that unfolded common proteins exhibit high affinity to surfaces and strong internal cohesion via amyloid-like aggregation in water. Using bovine serum albumin (BSA) as a model protein, we obtain a stable unfolded protein by cleaving the disulfide bonds and maintaining the unfolded state by means of stabilizing agents such as trifluoroethanol (TFE) and urea. The diffusion of stabilizing agents into water exposes the hydrophobic residues of an unfolded protein and initiates aggregation of the unfolded protein into a solid block. A robust and stable underwater glue can thus be prepared from tens of common proteins. This strategy deciphers a general code in common proteins to construct robust underwater glue from abundant biomass.
Switch of cell migration modes orchestrated by changes of three-dimensional lamellipodium structure and intracellular diffusion
Authors: Jiang Chao , Luo Hong-Yu , Xu Xinpeng , Dou Shuo-Xing , Li Wei , Guan Dongshi , Ye Fangfu , Chen Xiaosong , Guo Ming , Wang Peng-Ye , Li Hui 
Published: August 2023

AbstractCell migration plays important roles in many biological processes, but how migrating cells orchestrate intracellular molecules and subcellular structures to regulate their speed and direction is still not clear. Here, by characterizing the intracellular diffusion and the three-dimensional lamellipodium structures of fish keratocyte cells, we observe a strong positive correlation between the intracellular diffusion and cell migration speed and, more importantly, discover a switching of cell migration modes with reversible intracellular diffusion variation and lamellipodium structure deformation. Distinct from the normal fast mode, cells migrating in the newly-found slow mode have a deformed lamellipodium with swollen-up front and thinned-down rear, reduced intracellular diffusion and compartmentalized macromolecule distribution in the lamellipodium. Furthermore, in turning cells, both lamellipodium structure and intracellular diffusion dynamics are also changed, with left-right symmetry breaking. We propose a mechanism involving the front-localized actin polymerization and increased molecular crowding in the lamellipodium to explain how cells spatiotemporally coordinate the intracellular diffusion dynamics and the lamellipodium structure in regulating their migrations.
A qPCR technology for direct quantification of methylation in untreated DNA
Authors: Bendixen Kamilla Kolding , Mindegaard Maria , Epistolio Samantha , Dazio Giulia , Marchi Francesco , Spina Paolo , Arnspang Eva C. , Soerensen Mette , Christensen Ulf Bech , Frattini Milo , Petersen Rasmus Koefoed 
Published: August 2023

AbstractDNA methylation is important for gene expression and alterations in DNA methylation are involved in the development and progression of cancer and other major diseases. Analysis of DNA methylation patterns has until now been dependent on either a chemical or an enzymatic pre-treatment, which are both time consuming procedures and potentially biased due to incomplete treatment. We present a qPCR technology, EpiDirect®, that allows for direct PCR quantification of DNA methylations using untreated DNA. EpiDirect® is based on the ability of Intercalating Nucleic Acids (INA®) to differentiate between methylated and unmethylated cytosines in a special primer design. With this technology, we develop an assay to analyze the methylation status of a region of the MGMT promoter used in treatment selection and prognosis of glioblastoma patients. We compare the assay to two bisulfite-relying, methyl-specific PCR assays in a study involving 42 brain tumor FFPE samples, revealing high sensitivity, specificity, and the clinical utility of the method.
Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: the METS-microbiome study
Authors: Ecklu-Mensah Gertrude , Choo-Kang Candice , Maseng Maria Gjerstad , Donato Sonya , Bovet Pascal , Viswanathan Bharathi , Bedu-Addo Kweku , Plange-Rhule Jacob , Oti Boateng Prince , Forrester Terrence E. , Williams Marie , Lambert Estelle V. , Rae Dale , Sinyanya Nandipha , Luke Amy , Layden Brian T. , O’Keefe Stephen , Gilbert Jack A. , Dugas Lara R. 
Published: August 2023

AbstractThe relationship between microbiota, short chain fatty acids (SCFAs), and obesity remains enigmatic. We employ amplicon sequencing and targeted metabolomics in a large (n = 1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbiota diversity and fecal SCFAs are greatest in Ghanaians, and lowest in Americans, representing each end of the urbanization spectrum. Obesity is significantly associated with a reduction in SCFA concentration, microbial diversity, and SCFA synthesizing bacteria, with country of origin being the strongest explanatory factor. Diabetes, glucose state, hypertension, obesity, and sex can be accurately predicted from the global microbiota, but when analyzed at the level of country, predictive accuracy is only universally maintained for sex. Diabetes, glucose, and hypertension are only predictive in certain low-income countries. Our findings suggest that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries. Further investigation is needed to determine the factors driving this association.
RNAPII-dependent ATM signaling at collisions with replication forks
Authors: Einig Elias , Jin Chao , Andrioletti Valentina , Macek Boris , Popov Nikita 
Published: August 2023

AbstractDeregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and are thought to underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII nucleates activation of the ATM kinase at TRCs to stimulate DNA repair. We show the ATPase WRNIP1 associates with RNAPII and limits ATM activation during unperturbed cell cycle. WRNIP1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase HUWE1. Mutation of HUWE1 induces TRCs, promotes WRNIP1 dissociation from RNAPII and binding to the replisome, stimulating ATM recruitment and activation at RNAPII. TRCs and translocation of WRNIP1 are rapidly induced in response to hydroxyurea treatment to activate ATM and facilitate subsequent DNA repair. We propose that TRCs can provide a controlled mechanism for stalling of replication forks and ATM activation, instrumental in cellular response to replicative stress.
A synthetic cell-free 36-enzyme reaction system for vitamin B12 production
Authors: Kang Qian , Fang Huan , Xiang Mengjie , Xiao Kaixing , Jiang Pingtao , You Chun , Lee Sang Yup , Zhang Dawei 
Published: August 2023

AbstractAdenosylcobalamin (AdoCbl), a biologically active form of vitamin B12 (coenzyme B12), is one of the most complex metal-containing natural compounds and an essential vitamin for animals. However, AdoCbl can only be de novo synthesized by prokaryotes, and its industrial manufacturing to date was limited to bacterial fermentation. Here, we report a method for the synthesis of AdoCbl based on a cell-free reaction system performing a cascade of catalytic reactions from 5-aminolevulinic acid (5-ALA), an inexpensive compound. More than 30 biocatalytic reactions are integrated and optimized to achieve the complete cell-free synthesis of AdoCbl, after overcoming feedback inhibition, the complicated detection, instability of intermediate products, as well as imbalance and competition of cofactors. In the end, this cell-free system produces 417.41 μg/L and 5.78 mg/L of AdoCbl using 5-ALA and the purified intermediate product hydrogenobyrate as substrates, respectively. The strategies of coordinating synthetic modules of complex cell-free system describe here will be generally useful for developing cell-free platforms to produce complex natural compounds with long and complicated biosynthetic pathways.
SARS-CoV-2 vaccination elicits broad and potent antibody effector functions to variants of concern in vulnerable populations
Authors: Hederman Andrew P. , Natarajan Harini , Heyndrickx Leo , Ariën Kevin K. , Wiener Joshua A. , Wright Peter F. , Bloch Evan M. , Tobian Aaron A. R. , Redd Andrew D. , Blankson Joel N. , Rottenstreich Amihai , Zarbiv Gila , Wolf Dana , Goetghebuer Tessa , Marchant Arnaud , Ackerman Margaret E. 
Published: August 2023

AbstractSARS-CoV-2 variants have continuously emerged in the face of effective vaccines. Reduced neutralization against variants raises questions as to whether other antibody functions are similarly compromised, or if they might compensate for lost neutralization activity. Here, the breadth and potency of antibody recognition and effector function is surveyed following either infection or vaccination. Considering pregnant women as a model cohort with higher risk of severe illness and death, we observe similar binding and functional breadth for healthy and immunologically vulnerable populations, but considerably greater functional antibody breadth and potency across variants associated with vaccination. In contrast, greater antibody functional activity targeting the endemic coronavirus OC43 is noted among convalescent individuals, illustrating a dichotomy in recognition between close and distant human coronavirus strains associated with exposure history. This analysis of antibody functions suggests the differential potential for antibody effector functions to contribute to protecting vaccinated and convalescent subjects as novel variants continue to evolve.
Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice
Authors: Isidro-Hernández Marta , Casado-García Ana , Oak Ninad , Alemán-Arteaga Silvia , Ruiz-Corzo Belén , Martínez-Cano Jorge , Mayado Andrea , Sánchez Elena G. , Blanco Oscar , Gaspar Ma Luisa , Orfao Alberto , Alonso-López Diego , De Las Rivas Javier , Riesco Susana , Prieto-Matos Pablo , González-Murillo África , Criado Francisco Javier García , Cenador María Begoña García , Ramírez-Orellana Manuel , de Andrés Belén , Vicente-Dueñas Carolina , Cobaleda César , Nichols Kim E. , Sánchez-García Isidro 
Published: August 2023

AbstractThe initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children. Several preclinical studies have shown that exposure to immune stressors triggers the transformation of preleukemic B cells to full-blown B-ALL, but how this takes place is still a longstanding and unsolved challenge. Here we show that dysregulation of innate immunity plays a driving role in the clonal evolution of pre-malignantPax5+/−B-cell precursors toward leukemia. Transcriptional profiling reveals thatMyd88is downregulated in immune-stressed pre-malignant B-cell precursors and in leukemic cells. Genetic reduction ofMyd88expression leads to a significant increase in leukemia incidence inPax5+/−Myd88+/−mice through an inflammation-dependent mechanism. Early induction of Myd88-independent Toll-like receptor 3 signaling results in a significant delay of leukemia development inPax5+/−mice. Altogether, these findings identify a role for innate immunity dysregulation in leukemia, with important implications for understanding and therapeutic targeting of the preleukemic state in children.
Exploring anharmonic lattice dynamics and dielectric relations in niobate perovskites from first-principles self-consistent phonon calculations
Authors: Kim Kwangrae , Hwang Woohyun , Oh Seung-Hyun Victor , Soon Aloysius 
Published: August 2023

AbstractGroup I niobates (KNbO3 and NaNbO3) are promising lead-free alternatives for high-performance energy storage applications. Despite their potential, their complex phase transitions arising from temperature-dependent phonon softening and anharmonic effects on dielectric properties remain poorly explored. In this study, we employ density-functional theory (DFT) and self-consistent phonon (SCP) calculations to investigate finite-temperature phonons in cubic niobate perovskites. To include explicit anharmonic vibrational effects, SCP frequencies are shifted by the bubble self-energy correction within the quasiparticle (QP) approximation, providing precise descriptions of phonon softening in these strongly anharmonic solids. We further calculate the static dielectric constant of KNbO3 and NaNbO3 as a function of temperature using the Lyddane-Sachs-Teller (LST) relation and QP-corrected phonon dispersions. Our theoretical results align with experimental data, offering reliable temperature-dependent phonon dispersions while considering anharmonic self-energies and thermal expansion effects, enhancing our understanding of the complex relations between lattice vibrations and phase transitions in these anharmonic oxides.