Natural killer cell-mediated cytotoxicity shapes the clonal evolution of B cell leukaemia.

The term cancer immunoediting describes the dual role by which the immune system can suppress and promote tumour growth and is divided into three phases: elimination, equilibrium and escape. The role of NK cells has mainly been attributed to the elimination phase. Here we show that NK cells play a role in all three phases of cancer immunoediting.

Global Profiling of Protein Phosphorylation, Acetylation, and β-Hydroxybutyrylation in .

Protein post-translational modifications (PTMs) regulate protein functions but remain poorly characterized in . This study examined three PTMs: lysine acetylation (Kac), lysine β-hydroxybutyrylation (Kbhb), and phosphorylation. Using LC-MS/MS, we identified 4571 Kac sites, 7812 Kbhb sites, and 6237 phosphorylation sites across 2455, 3109, and 2786 proteins, respectively.

NEAT1 modulates the TIRR/53BP1 complex to maintain genome integrity.

Tudor Interacting Repair Regulator (TIRR) is an RNA-binding protein (RBP) that interacts directly with 53BP1, restricting its access to DNA double-strand breaks (DSBs) and its association with p53. We utilized iCLIP to identify RNAs that directly bind to TIRR within cells, identifying the long non-coding RNA NEAT1 as the primary RNA partner. The high affinity of TIRR for NEAT1 is due to prevalent G-rich motifs in the short isoform (NEAT1_1) region of NEAT1.

Distinguishing word identity and sequence context in DNA language models.

Transformer-based large language models (LLMs) are very suited for biological sequence data, because of analogies to natural language. Complex relationships can be learned, because a concept of "words" can be generated through tokenization. Training the models with masked token prediction, they learn both token sequence identity and larger sequence context.

Biomarker screen for efficacy of oncolytic virotherapy in patient-derived pancreatic cancer cultures.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking.

The activation of alpha amylase 2 by glutamine requires its N-terminal aspartate kinase-chorismate mutase-tyrA (ACT) domain.

The coordination of assimilation pathways for all the elements that make up cellular components is a vital task for every organism. Integrating the assimilation and use of carbon (C) and nitrogen (N) is of particular importance because of the high cellular abundance of these elements. Starch is one of the most important storage polymers of photosynthetic organisms, and a complex regulatory network ensures that biosynthesis and degradation of starch are coordinated with photosynthetic activity and growth.

The Role of in Ferroptosis and Apoptosis in Cancer.

Cysteine dioxygenase type 1 () is a tumor suppressor gene. It regulates the metabolism of cysteine, thereby influencing the cellular antioxidative capacity. This function puts in a prominent position to promote ferroptosis and apoptosis.

Knocking Out Chloroplastic Aldolases/Rubisco Lysine Methyltransferase Enhances Biomass Accumulation in under High-Light Stress.

Rubisco large-subunit methyltransferase (LSMT), a SET-domain protein lysine methyltransferase, catalyzes the formation of trimethyl-lysine in the large subunit of Rubisco or in fructose-1,6-bisphosphate aldolases (FBAs). Rubisco and FBAs are both vital proteins involved in CO fixation in chloroplasts; however, the physiological effect of their trimethylation remains unknown. In , a homolog of LSMT (NoLSMT) is found.

: Current Implications in Cardiovascular Diseases and Cancers.

Castor zinc finger 1 (CASZ1) is a C2H2 zinc finger family protein that has two splicing variants, CASZ1a and CASZ1b. It is involved in multiple physiological processes, such as tissue differentiation and aldosterone antagonism. Genetic and epigenetic alternations of have been characterized in multiple cardiovascular disorders, such as congenital heart diseases, chronic venous diseases, and hypertension.

OpenPBTA: The Open Pediatric Brain Tumor Atlas.

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors.

Characterization of histone acetyltransferases and deacetylases and their roles in response to dehydration stress in (Rhodophyta).

Histone acetylation is one of the most pivotal epigenetic mechanisms in eukaryotes and has been tightly linked to the regulation of various genes controlling growth, development and response to environmental stresses in both animals and plants. Till date, the association of histone acetylation to dehydration stress in red algae and genes encoding the enzymes responsible for histone acetylation: histone acetyltransferases (HATs) or histone deacetylases (HDACs), remains largely unknown. In this study, in silico analysis of the red seaweed identified 6 HAT genes and 10 HDAC genes.

Proteomic Research of Extracellular Vesicles in Clinical Biofluid.

Extracellular vesicles (EVs), the lipid bilayer membranous structures of particles, are produced and released from almost all cells, including eukaryotes and prokaryotes. The versatility of EVs has been investigated in various pathologies, including development, coagulation, inflammation, immune response modulation, and cell-cell communication. Proteomics technologies have revolutionized EV studies by enabling high-throughput analysis of their biomolecules to deliver comprehensive identification and quantification with rich structural information (PTMs, proteoforms).

ChIP-Based Nuclear DNA Isolation for Genome Sequencing in to Remove Cytosol and Bacterial DNA Contamination.

Contamination from cytosolic DNA (plastid and mitochondrion) and epiphytic bacteria is challenging the efficiency and accuracy of genome-wide analysis of nori-producing marine seaweed . Unlike bacteria and organellar DNA, nuclear DNA is closely associated with histone proteins. In this study, we applied Chromatin Immunoprecipitation (ChIP) of histone H3 to isolate nuclear DNA, followed by high-throughput sequencing.

The C-terminal region of phytoene synthase is a key element to control carotenoid biosynthesis in the haloarchaeon Haloferax volcanii.

Phytoene synthase (PSY) converts two molecules of geranyl-geranyl diphosphate to phytoene, the key regulatory step in carotenogenesis. However, post-translational mechanisms that control PSY expression are scarcely understood. Carotenoid biosynthesis (mainly bacterioruberin) is a distinctive feature of haloarchaea thriving in hypersaline environments.

MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation.

Rett syndrome is a human intellectual disability disorder that is associated with mutations in the X-linked gene. The epigenetic reader MeCP2 binds to methylated cytosines on the DNA and regulates chromatin organization. We have shown previously that Rett syndrome missense mutations are impaired in chromatin binding and heterochromatin reorganization.

Proteome Turnover Analysis in Haloferax volcanii by a Heavy Isotope Multilabeling Approach.

The cellular protein repertoire is highly dynamic and responsive to internal or external stimuli. Its changes are largely the consequence of the combination of protein synthesis and degradation, referred collectively as protein turnover. Different proteomics techniques have been developed to determine the whole proteome turnover of a cell, but very few have been applied to archaea.

ceRNA crosstalk mediated by ncRNAs is a novel regulatory mechanism in fish sex determination and differentiation.

Competing endogenous RNAs (ceRNAs) are vital regulators of gene networks in mammals. The involvement of noncoding RNAs (ncRNAs) as ceRNA in genotypic sex determination (GSD) and environmental sex determination (ESD) in fish is unknown. The Chinese tongue sole, which has both GSD and ESD mechanisms, was used to map the dynamic expression pattern of ncRNAs and mRNA in gonads during sex determination and differentiation.

Functional Genomics Uncovers Pleiotropic Role of Rhomboids in .

The physiological role of ubiquitous rhomboid proteases, membrane-integral proteins that cleave their substrates inside the lipid bilayer, is still ill-defined in many prokaryotes. The two rhomboid genes and of were mutated and it was the aim of this study to investigate consequences in respect to growth phenotype, stress resistance, transcriptome, proteome, and lipidome composition. Albeit increased amount of Cg2767 upon heat stress, its absence did not change the growth behavior of during exponential and stationary phase.

Encodes an Active Rhomboid Protease: Proteome Response after Gene Deletion.

Rhomboids are intramembrane serine proteases highly conserved in the three domains of life. Their key roles in eukaryotes are well understood but their contribution to bacterial physiology is still poorly characterized. Here we demonstrate that , the etiological agent of the zoonosis called brucellosis, encodes an active rhomboid protease capable of cleaving model heterologous substrates like Gurken and TatA.

Transitory ischemic attack associated with a rare fenestration of the cervical segment of the internal carotid artery: a case report.

Background: Fenestration of the cervical segment of the internal carotid artery is a very rare finding, and its origin is still not fully understood. Explanations of its genesis range from dissections leading to the fenestration to the more common interpretation as a developmental vascular variant. However, most reported cases were symptomatic and presented with dissections, where even endovascular treatment of the fenestration of the cervical segment of the internal carotid artery became necessary.

Evaluation of circulating Dickkopf-1 as a prognostic biomarker in ovarian cancer patients.

Objectives: Dickkopf-1 (DKK1) is a secreted protein, known for suppressing the differentiation and activity of bone-building osteoblasts by acting as an inhibitor of Wnt-signalling. Soluble DKK1 (sDKK1) has been proposed as prognostic biomarker for a wide range of malignancies, however, clinical relevance of sDKK1 as potential blood-based marker for ovarian cancer is unknown.

Methods: sDKK1 levels were quantified in a cohort of 150 clinically documented ovarian cancer patients by a commercially available DKK1 ELISA (Biomedica, Vienna, Austria).

Phylogenetic analysis of SARS-CoV-2 lineage development across the first and second waves in Eastern Germany in 2020: insights into the cause of the second wave.

In Germany, Eastern regions had a mild first wave of coronavirus disease 2019 (COVID-19) from March to May 2020, but were badly hit by a second wave later in autumn and winter. It is unknown how the second wave was initiated and developed in Eastern Germany where the number of COVID-19 cases was close to zero in June and July 2020. We used genomic epidemiology to investigate the dynamic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage development across the first and second waves in Eastern Germany.