Advancing Glass Engineering: Harnessing Focused Electron Beams for Direct Microstructuring.

A technological approach for direct glass structuring is presented by exploiting electron-beam-induced defect generation utilizing a conventional scanning electron microscope (SEM). The structuring process is assumed to be linked to electron-beam-induced ion migration and allows to create structures of several hundred nanometers in depth. It is demonstrated that the structuring can be realized in literally any SEM, which thus enables a comparatively simple implementation in support of a broad field of applications.

PRMT5 inhibition reduces hyperinflammation in a murine model of secondary hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but aggressive and potentially lethal hyperinflammatory syndrome characterized by pathologic immune activation and excessive production of proinflammatory cytokines leading to tissue damage and multisystem organ failure. There is an urgent need for the discovery of novel targets and development of therapeutic strategies to treat this rare but deadly syndrome. Protein arginine methyltransferase 5 (PRMT5) mediates T-cell-based inflammatory responses, making it a potential actionable target for the treatment of HLH.

Tip-Induced 3D Printing on the Nanoscale with Field Emission Scanning Probes.

3D printing down to the nanoscale remains a significant challenge. In this paper, the study explores the use of scanning probes that emit low-energy electrons (<100 eV) coupled with the localized injection and electron-induced decomposition of precursor molecules, for the precise localized deposition of 3D nanostructures. The experiments are performed inside the chamber of a scanning electron microscope (SEM), enabling the use of the in-built gas injector system (GIS) with gaseous naphthalene precursor for carbon deposition, as well as immediate inspection of the deposits by SEM.

Geographic EBV variants confound disease-specific variant interpretation and predict variable immune therapy responses.

Epstein-Barr virus (EBV) is a potent carcinogen linked to hematologic and solid malignancies and causes significant global morbidity and mortality. Therapy using allogeneic EBV-specific lymphocytes shows promise in certain populations, but the impact of EBV genome variation on these strategies remains unexplored. To address this, we sequenced 217 EBV genomes, including hematologic malignancies from Guatemala, Peru, Malawi, and Taiwan, and analyzed them alongside 1307 publicly available EBV genomes from cancer, nonmalignant diseases, and healthy individuals across Africa, Asia, Europe, North America, and South America.

Genotype characterization of Epstein-Barr virus among adults living with human immunodeficiency virus in Ethiopia.

Background: Epstein-Barr virus (EBV) is a human lymphotropic herpesvirus with a causative agent in cancer. There are two genotypes of EBV (EBV genotype 1 and EBV genotype 2) that have been shown to infect humans. This study aimed to characterize the EBV genotype among people with human immunodeficiency virus (PWH) and HIV-negative individuals in Ethiopia.

Detection and Quantification of the Epstein-Barr Virus in Lymphoma Patients from Ethiopia: Molecular and Serological Approaches.

The Epstein-Barr virus (EBV) is a known oncogenic virus associated with various lymphoma subtypes throughout the world. However, there is a lack of information regarding EBV prevalence in lymphoma patients, specifically in Ethiopia. This study aimed to investigate the presence of the EBV and determine its viral load in lymphoma patients from Ethiopia using molecular and serological approaches.

Resistance to PRMT5-targeted therapy in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma, and patients who relapse on targeted therapies have poor prognosis. Protein arginine methyltransferase 5 (PRMT5), an enzyme essential for B-cell transformation, drives multiple oncogenic pathways and is overexpressed in MCL. Despite the antitumor activity of PRMT5 inhibition (PRT-382/PRT-808), drug resistance was observed in a patient-derived xenograft (PDX) MCL model.

Genotypes Distribution of Epstein-Barr Virus among Lymphoma Patients in Ethiopia.

Epstein-Barr virus (EBV) is an oncogenic herpes virus associated with several human malignancies. Two main EBV genotypes (type 1 and type 2) distinguished by the differences in EBV nuclear antigens are known. Geographic variability in these genetic differences has been observed in the incidence of some EBV-related tumors.

The Burden of Epstein-Barr Virus (EBV) and Its Determinants among Adult HIV-Positive Individuals in Ethiopia.

Epstein-Barr virus (EBV) is a well-known risk factor for the development of nasopharyngeal carcinoma, Hodgkin's lymphoma (HL), and Non-Hodgkin's lymphoma (NHL). People with HIV infection (PWH) are at increased risk for EBV-associated malignancies such as HL and NHL. Nevertheless, there are limited data on the burden of EBV among this population group in Ethiopia.

Effect of Malaria Infection on Epstein-Barr Virus Persistence in Kenyan Children.

Background: The 2 cofactors in the etiology of Burkitt lymphoma (BL) are Epstein-Barr virus (EBV) and repeated Plasmodium falciparum malaria infections. This study evaluated EBV loads in mucosal and systemic compartments of children with malaria and controls. Age was analyzed as a covariate because immunity to malaria in endemic regions is age dependent.

Follicular Helper and Regulatory T Cells Drive the Development of Spontaneous Epstein-Barr Virus Lymphoproliferative Disorder.

Epstein-Barr virus (EBV) is a ubiquitous herpes virus associated with various cancers. EBV establishes latency with life-long persistence in memory B-cells and can reactivate lytic infection placing immunocompromised individuals at risk for EBV-driven lymphoproliferative disorders (EBV-LPD). Despite the ubiquity of EBV, only a small percentage of immunocompromised patients (~20%) develop EBV-LPD.

Disruption of Nurse-like Cell Differentiation as a Therapeutic Strategy for Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia, but, despite advances in treatment, many patients still experience relapse. CLL cells depend on interactions with supportive cells, and nurse-like cells (NLCs) are the major such cell type. However, little is known about how NLCs develop.

Identification and Targeting of the Developmental Blockade in Extranodal Natural Killer/T-cell Lymphoma.

Unlabelled: Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive, rare lymphoma of natural killer (NK) cell origin with poor clinical outcomes. Here we used phenotypic and molecular profiling, including epigenetic analyses, to investigate how ENKTL ontogeny relates to normal NK-cell development. We demonstrate that neoplastic NK cells are stably, but reversibly, arrested at earlier stages of NK-cell maturation.

Uncontrolled CD21 age-associated and B1 B cell accumulation caused by failure of an EGR2/3 tolerance checkpoint.

CD21 age-associated or atypical memory B cells are autoantibody enriched and poised for plasma cell differentiation. These cells overaccumulate in chronic infections, autoimmune disease, and immunodeficiency, posing the question of what checkpoints normally oppose their accumulation. Here, we reveal a critical role for paralogous calcium-NFAT-regulated transcription factors EGR2 and EGR3 that are induced in self-reactive B cells.

Acute Myeloid Leukemia Alters Group 1 Innate Lymphoid Cell Differentiation from a Common Precursor.

NK cells are known to be developmentally blocked and functionally inhibited in patients with acute myeloid leukemia (AML), resulting in poor clinical outcomes. In this study, we demonstrate that whereas NK cells are inhibited, closely related type 1 innate lymphoid cells (ILC1s) are enriched in the bone marrow of leukemic mice and in patients with AML. Because NK cells and ILC1s share a common precursor (ILCP), we asked if AML acts on the ILCP to alter developmental potential.

Putative Cooperative ATP-DnaA Binding to Double-Stranded DnaA Box and Single-Stranded DnaA-Trio Motif upon Replication Initiation Complex Assembly.

is a region of the bacterial chromosome at which the initiator protein DnaA interacts with specific sequences, leading to DNA unwinding and the initiation of chromosome replication. The general architecture of s is universal; however, the structure of and the mode of orisome assembly differ in distantly related bacteria. In this work, we characterized of , which consists of two DnaA box clusters and a DNA unwinding element (DUE); the latter can be subdivided into a GC-rich region, a DnaA-trio and an AT-rich region.

STK11/LKB1 Loss of Function Is Associated with Global DNA Hypomethylation and -Adenosyl-Methionine Depletion in Human Lung Adenocarcinoma.

STK11 (liver kinase B1, LKB1) is the fourth most frequently mutated gene in lung adenocarcinoma, with loss of function observed in up to 30% of all cases. Our previous work identified a 16-gene signature for LKB1 loss of function through mutational and nonmutational mechanisms. In this study, we applied this genetic signature to The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples and discovered a novel association between LKB1 loss and widespread DNA demethylation.

Identification of the Unwinding Region in the Chromosomal Origin of Replication.

Faithful DNA replication is crucial for viability of cells across all kingdoms. Targeting DNA replication is a viable strategy for inhibition of bacterial pathogens. is an important enteropathogen that causes potentially fatal intestinal inflammation.

gammaBOriS: Identification and Taxonomic Classification of Origins of Replication in Gammaproteobacteria using Motif-based Machine Learning.

The biology of bacterial cells is, in general, based on information encoded on circular chromosomes. Regulation of chromosome replication is an essential process that mostly takes place at the origin of replication (oriC), a locus unique per chromosome. Identification of high numbers of oriC is a prerequisite for systematic studies that could lead to insights into oriC functioning as well as the identification of novel drug targets for antibiotic development.

Epigenetic reprogramming sensitizes immunologically silent EBV+ lymphomas to virus-directed immunotherapy.

Despite advances in T-cell immunotherapy against Epstein-Barr virus (EBV)-infected lymphomas that express the full EBV latency III program, a critical barrier has been that most EBV+ lymphomas express the latency I program, in which the single Epstein-Barr nuclear antigen (EBNA1) is produced. EBNA1 is poorly immunogenic, enabling tumors to evade immune responses. Using a high-throughput screen, we identified decitabine as a potent inducer of immunogenic EBV antigens, including LMP1, EBNA2, and EBNA3C.

origin of chromosomal replication with two putative unwinding elements.

DNA replication is controlled mostly at the initiation step. In bacteria, replication of the chromosome starts at a single origin of replication called . The initiator protein, DnaA, binds to specific sequences (DnaA boxes) within and assembles into a filament that promotes DNA double helix opening within the DNA unwinding element (DUE).

Developmental subtypes assessed by DNA methylation-iPLEX forecast the natural history of chronic lymphocytic leukemia.

Alterations in global DNA methylation patterns are a major hallmark of cancer and represent attractive biomarkers for personalized risk stratification. Chronic lymphocytic leukemia (CLL) risk stratification studies typically focus on time to first treatment (TTFT), time to progression (TTP) after treatment, and overall survival (OS). Whereas TTFT risk stratification remains similar over time, TTP and OS have changed dramatically with the introduction of targeted therapies, such as the Bruton tyrosine kinase inhibitor ibrutinib.

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer.

Background: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA).

Results: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.