Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.

The TGF-β family ligand Nodal is an essential regulator of embryonic development, orchestrating key processes such as germ layer specification and body axis formation through activation of SMAD2/3-mediated signaling. Significantly, this activation requires the co-receptor Cripto-1. However, despite their essential roles in embryogenesis, the molecular mechanism through which Cripto-1 enables Nodal to activate the SMAD2/3 pathway has remained elusive.

Synergistic activity of Pitstop-2 and 1,6-hexanediol in aggressive human lung cancer cells.

Metastatic cancer cells undergo metabolic reprogramming, which involves changes in the metabolic fluxes, including endocytosis, nucleocytoplasmic transport, and mitochondrial metabolism, to satisfy their massive demands for energy, cell division, and proliferation compared to normal cells. We have previously demonstrated the ability of two different types of compounds to interfere with linchpins of metabolic reprogramming, Pitstop-2 and 1,6-hexanediol (1,6-HD). 1,6-HD disrupts glycolysis enzymes and mitochondrial function, enhancing reactive oxygen species production and reducing cellular ATP levels, while Pitstop-2 impedes clathrin-mediated endocytosis and small GTPases activity.

An engineered Palivizumab IgG2 subclass for synthetic gp130 and fas mediated signaling.

Recently, we phenocopied Interleukin (IL-)6 signaling using the dimerized single-chain variable fragment (scFv) derived from the respiratory syncytial virus (RSV) IgG1-antibody Palivizumab (PLHFc) to activate a Palivizumab anti-idiotypic nanobody (AIP)-gp130 receptor fusion protein. Palivizumab was unable to activate STAT3 signaling, so we aimed to create a similar ligand capable of triggering this pathway. Here, we created three variants of the ligand called PLH0Fc, PLH4Fc and PLH8Fc by shortening the spacer region connecting PLH and Fc from 23 amino acids in PLHFc to 0 amino acids or expanding it by rigid linkers of 4 or 8 alpha helical loops, respectively.

Activation of sphingosine-1-phosphate receptor 2 (S1PR2) upregulates dihydropyrimidine dehydrogenase (DPD) expression in colon cancer cells.

Introduction: Dihydropyrimidine dehydrogenase (DPD) is a major determinant of cancer 5-fluorouracyl (5-FU) resistance via its direct degradation. However, the mechanisms of tumoral DPD upregulation have not been fully understood.

Objectives: This study aimed to explore the role of S1PR2 in the regulation of tumoral DPD expression, identifying S1PR2 as the potential target for reversing 5-FU resistance.

Testing the kinetic tradeoff between bicarbonate versus phosphoenolpyruvate affinity and glucose-6 phosphate response of phosphoenolpyruvate carboxylase from two C grasses.

Phosphoenolpyruvate (PEP) carboxylase (PEPC) has an anaplerotic role in central plant metabolism but also initiates the carbon concentrating mechanism during C photosynthesis. The C PEPC has different binding affinities (K) for PEP (K) and HCO (K), and allosteric regulation by glucose-6-phosphate (G6-P) compared to non-photosynthetic isoforms. These differences are linked to specific changes in amino acids within PEPC.

Metabolic and inflammatory status in prepuberty and early adulthood for individuals with a history of extrauterine growth restriction: a cohort study.

Background: Perinatal growth and nutrition have been shown to be determinants in the programming of different tissues, such as adipose tissue, predisposing individuals to metabolic alterations later in life. Previous studies have documented an increased risk of metabolic disturbances and low-grade inflammation in prepubertal children with a history of extrauterine growth restriction (EUGR). The aim of this study was to evaluate possible alterations resulting from impaired growth during early childhood and their impact on young adult health.

Independent effect of body fat content on inflammatory biomarkers in children and adolescents: The GENOBOX study.

Background And Aims: To assess the relationship between body composition indicators and inflammatory biomarkers in children and adolescents of the GENOBOX study.

Methods And Results: Anthropometry data from 264 subjects from the subsample of Zaragoza (Spain) included: weight, height, waist circumference, body mass index and triponderal index. Body composition was determined by Dual-energy X-ray Absorptiometry (DXA), obtaining visceral adipose tissue, fat mass index and lean mass index.

Deletion of metal transporter Zip14 reduces major histocompatibility complex II expression in murine small intestinal epithelial cells.

Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation.

Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.

DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown.

SEE: A Method for Predicting the Dynamics of Chromatin Conformation Based on Single-Cell Gene Expression.

The dynamics of chromatin conformation involve continuous and reversible changes within the nucleus of a cell, which participate in regulating processes such as gene expression, DNA replication, and damage repair. Here, SEE is introduced, an artificial intelligence (AI) method that utilizes autoencoder and transformer techniques to analyze chromatin dynamics using single-cell RNA sequencing data and a limited number of single-cell Hi-C maps. SEE is employed to investigate chromatin dynamics across different scales, enabling the detection of (i) rearrangements in topologically associating domains (TADs), and (ii) oscillations in chromatin interactions at gene loci.

Genetic and biochemical characterization of a radical SAM enzyme required for post-translational glutamine methylation of methyl-coenzyme M reductase.

Methyl-coenzyme M reductase (MCR), the key catalyst in the anoxic production and consumption of methane, contains an unusual 2-methylglutamine residue within its active site. data show that a B12-dependent radical SAM (rSAM) enzyme, designated MgmA, is responsible for this post-translational modification (PTM). Here, we show that two different MgmA homologs are able to methylate MCR when expressed in , an organism that does not normally possess this PTM.

Maize Streak Virus: Single and Gemini Capsid Architecture.

are ssDNA plant viruses whose control has both economical and agricultural importance. Their capsids assemble into two distinct architectural forms: (i) a T = 1 icosahedral and (ii) a unique twinned quasi-isometric capsid. Described here are the high-resolution structures of both forms of the maize streak virus using cryo-EM.

The Activity of 1,8-Dihydroanthraquinone Derivatives in Nervous System Cancers.

Primary and metastatic tumors of the nervous system represent a diverse group of neoplasms, each characterized by distinct biological features, prognostic outcomes, and therapeutic approaches. Due to their molecular complexity and heterogeneity, nervous system cancers (NSCs) pose significant clinical challenges. For decades, plants and their natural products with established anticancer properties have played a pivotal role in the treatment of various medical conditions, including cancers.

Proteomics: An Essential Tool to Study Plant-Specialized Metabolism.

Plants are a valuable source of specialized metabolites that provide a plethora of therapeutic applications. They are natural defenses that plants use to adapt and respond to their changing environment. Decoding their biosynthetic pathways and understanding how specialized plant metabolites (SPMs) respond to biotic or abiotic stress will provide vital knowledge for plant biology research and its application for the future sustainable production of many SPMs of interest.

Probing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.

Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence.

Immobile Integrin Signaling Transit and Relay Nodes Organize Mechanosignaling through Force-Dependent Phosphorylation in Focal Adhesions.

Transmembrane signaling receptors, such as integrins, organize as nanoclusters that provide several advantages, including increasing avidity, sensitivity (increasing the signal-to-noise ratio), and robustness (signaling threshold) of the signal in contrast to signaling by single receptors. Furthermore, compared to large micron-sized clusters, nanoclusters offer the advantage of rapid turnover for the disassembly of the signal. However, whether nanoclusters function as signaling hubs remains poorly understood.

Higher physical activity levels are related to faecal microbiota diversity and composition in young adults.

Increasing physical activity (PA) is recognised as an efficacious approach for preventing and treating cardiometabolic diseases. Recently, the composition of microorganisms living within the gut has been proposed as an important appropriate target for treating these diseases. Whether PA is related to faecal microbiota diversity and composition in humans remains to be ascertained.

The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

Integrated Analysis of Methylome and Transcriptome Responses to Exercise Training in Children with Overweight/Obesity.

We examined the effects of a 20-week exercise intervention on whole-blood genome-wide DNA methylation signature and its association with the exercise-induced changes in gene expression profiles in boys and girls with overweight/obesity (OW/OB). Twenty-three children (10.05 ± 1.

Serum and plasma as a good candidates of body fluids for detection lung cancer by FTIR liquid biopsy.

Using Fourier Transform Infrared spectroscopy (FTIR), it is possible to show chemical composition of materials and / or profile chemical changes occurring in tissues, cells, and body fluids during onset and progression of diseases. For diagnostic application, the use of blood would be the most appropriate in biospectroscopy studies since, (i) it is easily accessible and, (ii) enables frequent analyses of biochemical changes occurring in pathological states. At present, different studies have investigated potential of serum, plasma and sputum being alternative biofluids for lung cancer detection using FTIR.

SCREEN: A Graph-based Contrastive Learning Tool to Infer Catalytic Residues and Assess Enzyme Mutations.

Unlabelled: The accurate identification of catalytic residues contributes to our understanding of enzyme functions in biological processes and pathways. The increasing number of protein sequences necessitates computational tools for the automated prediction of catalytic residues in enzymes. Here, we introduce SCREEN, a graph neural network for the high-throughput prediction of catalytic residues via the integration of enzyme functional and structural information.

Tracing Sentinel Lymph Nodes and Inhibiting Lymphatic Metastasis with TiN Nanobipyramids Through Photothermal Therapy.

Background: The lymphatic system is the major route of cancer metastasis, and sentinel lymph nodes (SLNs) are the first station for the spread of cancer cells. Accurate identification of SLNs by tracers during surgery is crucial for SLN biopsy and lymphadenectomy. However, conventional monomodal tracers such as blue dyes and carbon nanoparticles often induce a misjudgment of SLNs and thus are still unsatisfying for clinical applications.

Phenotypic screens identify SCAF1 as critical activator of RNAPII elongation and global transcription.

Transcripts produced by RNA polymerase II (RNAPII) are fundamental for cellular responses to environmental changes. It is therefore no surprise that there exist multiple avenues for the regulation of this process. To explore the regulation mediated by RNAPII-interacting proteins, we used a small interfering RNA (siRNA)-based screen to systematically evaluate their influence on RNA synthesis.

PGRN protects against serum deprivation-induced cell death by promoting the ROS scavenger system in cervical cancer.

Progranulin (PGRN), an autocrine growth factor with tumorigenic roles in a variety of tumors, is a putative survival factor for normal and cancer cells in vitro. However, the fundamental mechanism of PGRN-mediated survival of cancer cells suffering from various types of microenvironmental stresses, such as serum deprivation, remains unknown. We show here that serum deprivation decreases intracellular PGRN protein levels in cervical cancer cells.