Interplay between genetics and epigenetics in lung fibrosis.

Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms.

Integration of vanHAX downstream of a ribosomal RNA operon restores vancomycin resistance in a susceptible Enterococcus faecium strain.

During the genomic characterisation of Enterococcus faecium strains (n = 39) collected in a haematology ward, we identified an isolate (OI25), which contained vanA-type vancomycin resistance genes but was phenotypically susceptible to vancomycin. OI25 could revert to resistance when cultured in the presence of vancomycin and was thus considered to be vancomycin-variable. Long-read sequencing was used to identify structural variations within the vancomycin resistance region of OI25 and to uncover its resistance reversion mechanism.

SLC1A5 is a key regulator of glutamine metabolism and a prognostic marker for aggressive luminal breast cancer.

Cancer cells exhibit altered metabolism, often relying on glutamine (Gln) for growth. Breast cancer (BC) is a heterogeneous disease with varying clinical outcomes. We investigated the role of the amino acid transporter SLC1A5 (ASCT2) and its association with BC subtypes and patient outcomes.

Botulinum neurotoxins exploit host digestive proteases to boost their oral toxicity via activating OrfXs/P47.

Botulinum neurotoxins (BoNTs) rank among the most potent toxins and many of them are produced by bacteria carrying the orfX gene cluster that also encodes four nontoxic proteins (OrfX1, OrfX2, OrfX3 and P47). The orfX gene cluster is also found in the genomes of many non-BoNT-producing bacteria, often alongside genes encoding oral insecticidal toxins. However, the functions of these OrfXs and P47 remain elusive.

Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature.

Isocitrate dehydrogenase wild-type glioblastoma (GBM) is characterised by a heterogeneous genetic landscape resulting from dynamic competition between tumour subclones to survive selective pressures. Improvements in metabolite identification and metabolome coverage have led to increased interest in clinically relevant applications of metabolomics. Here, we use liquid chromatography-mass spectrometry and gene expression microarray to profile integrated intratumour metabolic heterogeneity, as a direct functional readout of adaptive responses of subclones to the tumour microenvironment.

Plague in Small Mammals From an Endemic Focus of the Malagasy Central Highlands: A Longitudinal Survey With a Special Reference on Black Rats (Rattus rattus).

Plague, a zoonotic disease caused by Yersinia pestis, remains a major public health threat in several parts of the world, including Madagascar. Factors underlying long-term persistence and emergence of the pathogen remain poorly understood. We implemented a longitudinal survey to provide insights into plague reservoir ecology within an endemic focus.

Insulin-like Growth Factor 1 (IGF1) and Its Isoforms: Insights into the Mechanisms of Endometrial Cancer.

Endometrial cancer (EC) is a common gynaecological malignancy associated with metabolic dysfunctions such as obesity, diabetes and insulin resistance, as well as hormonal imbalances, particularly involving oestrogen and progesterone. These factors disrupt normal cellular metabolism, heightening the risk of developing endometrioid EC (EEC), the most prevalent subtype of EC. The insulin-like growth factor-1 (IGF1) pathway, a key regulator of growth, metabolism, and organ function, is implicated in EC progression.

Identification of Transcriptional Regulators of Immune Evasion Across Cancers: An Alternative Immunotherapeutic Strategy for Cholangiocarcinoma.

Background: Cancer immune evasion is a multifaceted process that synchronizes pro-tumoral immune infiltration, immunosuppressive inflammation, and inhibitory immune checkpoint expression (IC). Current immunotherapies combat this issue by reinstating immunosurveillance of tumors; however, it benefits a limited patient population. Thus, a more effective immunotherapeutic strategy is warranted to cater to specific patient populations.

The Detoxification Effects of Melatonin on Aflatoxin-Caused Toxic Effects and Underlying Molecular Mechanisms.

Aflatoxins (AFTs) are a form of mycotoxins mainly produced by and , which are common contaminants in various agricultural sources such as feed, milk, food, and grain crops. Aflatoxin B1 (AFB1) is the most toxic one among all AFTs. AFB1 undergoes bioactivation into AFB1-8,9-epoxide, then leads to diverse harmful effects such as neurotoxicity, carcinogenicity, hepatotoxicity, reproductive toxicity, nephrotoxicity, and immunotoxicity, with specific molecular mechanisms varying in different pathologies.

A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair.

Articular cartilage has limited capacity for repair (or for regeneration) under pathological conditions, given its non-vascularized connective tissue structure and low cellular density. Our group has successfully developed an injectable hydrogel for cartilage repair, composed of collagen type I (Col I), collagen type II (Col II), and methacrylated-hyaluronic acid (MeHA), capable of supporting chondrogenic differentiation of mesenchymal stem cells (MSCs) towards articular cartilage-like phenotypes. Recent studies have demonstrated that silencing may be an effective approach in promoting improved MSC chondrogenesis.

Interfacial water confers transcription factors with dinucleotide specificity.

Transcription factors (TFs) recognize specific bases within their DNA-binding motifs, with each base contributing nearly independently to total binding energy. However, the energetic contributions of particular dinucleotides can deviate strongly from the additive approximation, indicating that some TFs can specifically recognize DNA dinucleotides. Here we solved high-resolution (<1 Å) structures of MYF5 and BARHL2 bound to DNAs containing sets of dinucleotides that have different affinities to the proteins.

Quorum sensing signals of the grapevine crown gall bacterium, sp. Rr2-17: use of inducible expression and polymeric resin to sequester acyl-homoserine lactones.

Background: A grapevine crown gall tumor strain, sp. strain Rr2-17 was previously reported to accumulate copious amounts of diverse quorum sensing signals during growth. Genome sequencing identified a single luxI homolog in strain Rr2-17, suggesting that it may encode for a AHL synthase with broad substrate range, pending functional validation.

VGLL-fusions define a new class of intraparenchymal CNS schwannoma.

Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.

Monitoring central nervous system tumour metabolism using cerebrospinal fluid.

Central nervous system (CNS) tumours are the most common cancer cause of death in under 40s in the UK, largely because they persist and recur and sometimes metastasise during treatment. Therefore, longitudinal monitoring of patients during and following treatment must be undertaken to understand the course of the disease and alter treatment plans reactively. This monitoring must be specific, sensitive, rapid, low cost, simple, and accepted by the patient.

Altered metabolic function induced by Aβ-oligomers and PSEN1 mutations in iPSC-derived astrocytes.

Altered energy metabolism in Alzheimer's disease (AD) is a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are implicated in multiple neurodegenerative diseases. Although numerous studies have investigated global changes in brain metabolism, redox status, gene expression and epigenetic markers in AD, the intricate interplay between different metabolic processes, particularly in astrocytes, remains poorly understood.

Protocol for the synthesis and activation of hydrogels with photocaged oligonucleotides.

Hydrogels with spatial-temporal control over chemical and physical properties allow for the creation of cellular niches with controllable properties that better mimic tissue environments. Here, we present a protocol for synthesizing hydrogels incorporating photocaged oligonucleotides that can be activated with non-ultraviolet (UV) wavelengths. We detail the synthesis of bulk hydrogels and spatially defined hydrogels with different chemical functionalities that all share common photocaged DNA.

Early career member highlights from the 22nd ERS Lung Science Conference: development of chronic lung diseases - from life-spanning mechanisms to preventive therapy.

https://bit.ly/4cbMjpS.

A Dynamic Model for Early Prediction of Alzheimer's Disease by Leveraging Graph Convolutional Networks and Tensor Algebra.

Alzheimer's disease (AD) is a neurocognitive disorder that deteriorates memory and impairs cognitive functions. Mild Cognitive Impairment (MCI) is generally considered as an intermediate phase between normal cognitive aging and more severe conditions such as AD. Although not all individuals with MCI will develop AD, they are at an increased risk of developing AD.

The more stars, the brighter! Interview with the ECM award winner 2023.

https://bit.ly/4f0AiVY.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.