Chronic viral mimicry induction following p53 loss promotes immune evasion.

Epigenetic therapies facilitate transcription of immunogenic repetitive elements that cull cancer cells through 'viral mimicry' responses. Paradoxically, cancer-initiating events also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood.

Viral mimicry evasion: a new role for oncogenic KRAS mutations.

"Viral mimicry" refers to the induction of an innate immune response and interferon signaling by endogenous stimuli such as double-stranded RNA (dsRNA). This response has been shown to have strong cancer therapeutic potential, including by enhancing the effectiveness of immune checkpoint inhibition (ICI) therapies, and may represent a tumor suppression mechanism that needs to be overcome for malignant transformation to proceed. In a recent study, Zhou and colleagues identify KRAS, a frequently mutated oncogene, as a negative regulator of dsRNA and viral mimicry in an ICI-resistant colorectal cancer model.

Cancer cells restrict immunogenicity of retrotransposon expression via distinct mechanisms.

To thrive, cancer cells must navigate acute inflammatory signaling accompanying oncogenic transformation, such as via overexpression of repeat elements. We examined the relationship between immunostimulatory repeat expression, tumor evolution, and the tumor-immune microenvironment. Integration of multimodal data from a cohort of pancreatic ductal adenocarcinoma (PDAC) patients revealed expression of specific Alu repeats predicted to form double-stranded RNAs (dsRNAs) and trigger retinoic-acid-inducible gene I (RIG-I)-like-receptor (RLR)-associated type-I interferon (IFN) signaling.

Pollution control and biodiesel production with microalgae: new perspectives on the use of flat panel photobioreactors regarding variation in volume application rate.

In the present study, the microalga Arthrospira platensis DHR 20 was cultivated in vertical flat-plate photobioreactors (FPBRs) to bioremediate anaerobically digested cattle wastewater (ACWW) and used as a growth substrate. The final objective was to evaluate the properties of the oil extracted from this biomass to determine its potential for biodiesel production. The process was divided into five phases, varying the volume of the applied substrate: 1 L (Phase I), 5 L (Phase II), 10 L (Phase III), 15 L (Phase IV), and 20 L (Phase V).

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions.

Functional genomic screens in two-dimensional cell culture models are limited in identifying therapeutic targets that influence the tumor microenvironment. By comparing targeted CRISPR-Cas9 screens in a two-dimensional culture with xenografts derived from the same cell line, we identified MEN1 as the top hit that confers differential dropout effects in vitro and in vivo. MEN1 knockout in multiple solid cancer types does not impact cell proliferation in vitro but significantly promotes or inhibits tumor growth in immunodeficient or immunocompetent mice, respectively.

Investigating antimicrobial-resistant bacteria from exotic domestic birds - a One Health concern.

Antimicrobial resistance is a natural mechanism in microorganisms, making the treatment of infections more complex in human and veterinary medicine. Global exotic and ornamental bird markets have significantly increased, and the close relationship between pets and humans makes exploring the potential role of these birds as vectors for the spread of antimicrobial-resistant bacteria imperative. This study aimed to use culture-dependent methods to investigate cloacal bacteria and the presence of antibiotic-resistant bacteria in four breeding stocks of ornamental birds.

Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer.

Viral mimicry describes the immune response induced by endogenous stimuli such as double-stranded RNA (dsRNA) from endogenous retroelements. Activation of viral mimicry has the potential to kill cancer cells or augment anti-tumor immune responses. Here, we systematically identify mechanisms of viral mimicry adaptation associated with cancer cell dependencies.

Modeling methyl-sensitive transcription factor motifs with an expanded epigenetic alphabet.

Background: Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription factors can distinguish between unmodified and modified bases. Current models of transcription factor binding tend not to take DNA modifications into account, while the recent few that do often have limitations.

Ratio of stemness to interferon signalling as a biomarker and therapeutic target of myeloproliferative neoplasm progression to acute myeloid leukaemia.

Progression to aggressive secondary acute myeloid leukaemia (sAML) poses a significant challenge in the management of myeloproliferative neoplasms (MPNs). Since the physiopathology of MPN is closely linked to the activation of interferon (IFN) signalling and that AML initiation and aggressiveness is driven by leukaemia stem cells (LSCs), we investigated these pathways in MPN to sAML progression. We found that high IFN signalling correlated with low LSC signalling in MPN and AML samples, while MPN progression and AML transformation were characterized by decreased IFN signalling and increased LSC signature.

Novel Variant of in a Compound Heterozygous Brazilian Girl with Hereditary Hypophosphatemic Rickets with Hypercalciuria.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare FGF23-independent disorder caused by biallelic variants in the gene. The disease severity varies, and patients have an increased risk of developing renal complications. Phosphate supplementation is standard of care and active vitamin D analogs are not indicated as they could worsen the hypercalciuria.

The chromatin and single-cell transcriptional landscapes of CD4 T cells in inflammatory bowel disease link risk loci with a proinflammatory Th17 cell population.

Introduction: The imbalance between Th17 and regulatory T cells in inflammatory bowel diseases (IBD) promotes intestinal epithelial cell damage. In this scenario, T helper cell lineage commitment is accompanied by dynamic changes to the chromatin that facilitate or repress gene expression.

Methods: Here, we characterized the chromatin landscape and heterogeneity of intestinal and peripheral CD4 T cellsfrom IBD patients using in house ATAC-Seq and single cell RNA-Seq libraries.

macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma.

Self-renewal is a crucial property of glioblastoma cells that is enabled by the choreographed functions of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could therefore represent an important step toward developing effective treatments for this universally lethal cancer. Here we uncover an epigenetic axis of self-renewal mediated by the histone variant macroH2A2.

Disentangling the Taxonomy, Systematics, and Life History of the Spider-Parasitic Fungus (Cordycipitaceae, Hypocreales).

(Cordycipitaceae, Hypocreales) is frequently observed growing on spiders, but little is known about their host range. One of the greatest challenges in describing these interactions is identifying the host, since the fungus often rapidly consumes the parasitised spiders and destroys important diagnostic taxonomic traits. Additionally, the global diversity of remains unclear, as does the natural history and phylogenetic relationships of most of the species.

Monocytes presenting a pro-inflammatory profile persist in patients submitted to a long-term pharmacological treatment after acute myocardial infarction.

Although it is broadly known that monocyte recruitment is involved in atherosclerosis development and that, in accordance with the microenvironment, these cells can be modulated into three well-known subpopulations: Classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16++), the effects of treatment with different pharmacological strategies (based on lipid-lowering and antiplatelets) after acute myocardial infarction upon the monocytes modulation and the role of the chemokine receptors CCR2, CCR5 and CX3CR1 in this context, are poorly understood. In this study, patients [n = 148, both men (n = 105, 71%) and women (n = 43, 29%)] submitted to treatment with a 2×2 factorial design, in which they received rosuvastatin 20 mg or simvastatin 40 mg plus ezetimibe 10 mg, as well as ticagrelor 90 mg or clopidogrel 75 mg were enrolled. Monocyte subsets were analyzed by flow cytometry at baseline (BL), and after one (1-M) and 6 months (6-M) of treatment.

Cerebrospinal fluid methylome-based liquid biopsies for accurate malignant brain neoplasm classification.

Background: Resolving the differential diagnosis between brain metastases (BM), glioblastomas (GBM), and central nervous system lymphomas (CNSL) is an important dilemma for the clinical management of the main three intra-axial brain tumor types. Currently, treatment decisions require invasive diagnostic surgical biopsies that carry risks and morbidity. This study aimed to utilize methylomes from cerebrospinal fluid (CSF), a biofluid proximal to brain tumors, for reliable non-invasive classification that addresses limitations associated with low target abundance in existing approaches.

Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction.

Small-cell lung cancer (SCLC) methylome is understudied. Here, we comprehensively profile SCLC using cell-free methylated DNA immunoprecipitation followed by sequencing (cfMeDIP-seq). Cell-free DNA (cfDNA) from plasma of 74 patients with SCLC pre-treatment and from 20 non-cancer participants, genomic DNA (gDNA) from peripheral blood leukocytes from the same 74 patients, and 7 accompanying circulating tumor cell-derived xenografts (CDXs) underwent cfMeDIP-seq.

The cell-free DNA methylome captures distinctions between localized and metastatic prostate tumors.

Metastatic prostate cancer remains a major clinical challenge and metastatic lesions are highly heterogeneous and difficult to biopsy. Liquid biopsy provides opportunities to gain insights into the underlying biology. Here, using the highly sensitive enrichment-based sequencing technology, we provide analysis of 60 and 175 plasma DNA methylomes from patients with localized and metastatic prostate cancer, respectively.

Endogenous retroelements as alarms for disruptions to cellular homeostasis.

Endogenous retroelements are DNA sequences which can duplicate and move to new locations in the genome. Actively moving endogenous retroelements can be disruptive to the host, and their expression is therefore often repressed. Interestingly, drugs that disrupt the repression of endogenous retroelements show promise for treating cancer.

Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls.

Cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) identifies genomic regions with DNA methylation, using a protocol adapted to work with low-input DNA samples and with cell-free DNA (cfDNA). We developed a set of synthetic spike-in DNA controls for cfMeDIP-seq to provide a simple and inexpensive reference for quantitative normalization. We designed 54 DNA fragments with combinations of methylation status (methylated and unmethylated), fragment length (80 bp, 160 bp, 320 bp), G + C content (35%, 50%, 65%), and fraction of CpG dinucleotides within the fragment (1/80 bp, 1/40 bp, 1/20 bp).

Metagenome-Assembled Genomes of from Kombucha Exposed to Mars-Like Conditions Reveal the Secrets in Tolerating Extraterrestrial Stresses.

Kombucha mutualistic community (KMC) is composed by acetic acid bacteria and yeasts, producing fermented tea with health benefits. As part of the BIOlogy and Mars EXperiment (BIOMEX) project, the effect of Mars-like conditions on the KMC was analyzed. Here, we analyzed metagenome-assembled genomes (MAGs) of the , which is a predominant genus in KMC, to understand their roles in the KMC after exposure to Mars-like conditions (outside the International Space Station) based on functional genetic elements.

Metagenome Analysis Reveals a Response of the Antibiotic Resistome to Mars-like Extraterrestrial Conditions.

The spread of antibiotic resistance is becoming a serious global health concern. Numerous studies have been done to investigate the dynamics of antibiotic resistance genes (ARGs) in both indoor and outdoor environments. Nonetheless, few studies are available about the dynamics of the antibiotic resistome (total content of ARGs in the microbial cultures or communities) under stress in outer space environments.