The transposable element-derived transcript of LIN28B has a placental origin and is not specific to tumours.

Transposable elements (TEs) are genetic elements that have evolved as crucial regulators of human development and cancer, functioning as both genes and regulatory elements. When TEs become dysregulated in cancer cells, they can serve as alternate promoters to activate oncogenes, a process known as onco-exaptation. This study aimed to explore the expression and epigenetic regulation of onco-exaptation events in early human developmental tissues.

Embedded 3D Printing of Architected Ceramics via Microwave-Activated Polymerization.

Light- and ink-based 3D printing methods have vastly expanded the design space and geometric complexity of architected ceramics. However, light-based methods are typically confined to a relatively narrow range of preceramic and particle-laden resins, while ink-based methods are limited in geometric complexity due to layerwise assembly. Here, embedded 3D printing is combined with microwave-activated curing to generate architected ceramics with spatially controlled composition in freeform shapes.

Embedded 3D Printing of Multimaterial Polymer Lattices via Graph-Based Print Path Planning.

Recent advances in computational design and 3D printing enable the fabrication of polymer lattices with high strength-to-weight ratio and tailored mechanics. To date, 3D lattices composed of monolithic materials have primarily been constructed due to limitations associated with most commercial 3D printing platforms. Here, freeform fabrication of multi-material polymer lattices via embedded three-dimensional (EMB3D) printing is demonstrated.

Editing of DNA Methylation Patterns Using CRISPR-Based Tools.

DNA methylation is an epigenetic modification with an established role in both normal cellular function and mammalian disease. Despite well-characterized associations between aberrant DNA methylation changes and gene expression, evidence for a causal relationship in this context has been difficult to obtain. Early techniques for interrogating the role of DNA methylation in the regulation of gene transcription lack specificity and, where more specific techniques such and ZNFs and TALEs have been developed, they are limited by their extensive cost and labor requirements.

Next-Generation Bisulfite Sequencing for Targeted DNA Methylation Analysis.

Bisulfite sequencing is the "gold-standard" technique for DNA methylation analysis. By combining bisulfite sequencing with high-throughput, next-generation sequencing technology, we can document methylation from many thousands of individual reads (equivalent to alleles or "cells"), for multiple target regions and from many samples simultaneously. Here, we describe a next-generation bisulfite-sequencing assay for targeted DNA methylation analysis which offers scope for the simultaneous interrogation of multiple genomic loci across numerous samples.

Epigenetic basis and targeting of cancer metastasis.

Despite the development of novel therapeutic approaches and improved clinical management, survival from metastatic disease remains poor. Indeed, metastasis accounts for the vast majority of cancer-related deaths. The metastatic cascade comprises a complex range of molecular events that cannot be explained by genetic aberrations alone; dynamic, epigenetic regulatory mechanisms are now being implicated as key drivers of successful metastasis.

Locus-Specific DNA Methylation Editing in Melanoma Cell Lines Using a CRISPR-Based System.

DNA methylation is a key epigenetic modification implicated in the pathogenesis of numerous human diseases, including cancer development and metastasis. Gene promoter methylation changes are widely associated with transcriptional deregulation and disease progression. The advent of CRISPR-based technologies has provided a powerful toolkit for locus-specific manipulation of the epigenome.

Identification and validation of DNA methylation changes in pre-eclampsia.

Introduction: Pre-eclampsia (PE) is a dangerous placental condition that can lead to premature labour, seizures and death of mother and infant. Several studies have identified altered placental DNA methylation in PE; however, there is widespread inconsistency between studies and most findings have not been replicated. This study aimed to identify and validate consistent differences in methylation across multiple PE cohorts.

Hairpin-bisulfite sequencing of cells exposed to decitabine documents the process of DNA demethylation.

Although the mechanism of DNA demethylating drugs has been understood for many years, the direct effect of these drugs on methylation of the complementary strands of DNA has not been formally demonstrated. By using hairpin-bisulphite sequencing, we describe the kinetics and pattern of DNA methylation following treatment of cells by the DNA methyltransferase 1 (DNMT1) inhibitor, decitabine. As expected, we demonstrate complete loss of methylation on the daughter strand following S-phase in selected densely methylated genes in synchronized Jurkat cells.

Silencing of Testin expression is a frequent event in spontaneous lymphomas from Trp53-mutant mice.

The tumour suppressor gene, TES, is frequently methylated in many human tumours. Previously, we demonstrated that TES promoter methylation and transcriptional silencing was the most common molecular abnormality detected in childhood acute lymphoblastic leukaemia (ALL). Trp53-mutant mouse models predominantly develop B- and T-cell lymphomas, which are widely considered equivalent to childhood T and B ALL.

Promoter DNA Hypermethylation and Paradoxical Gene Activation.

DNA methylation is a stable epigenetic modification that contributes to the spatiotemporal regulation of gene expression. The manner in which DNA methylation contributes to transcriptional control is dependent on the biological context, including physiological state and the properties of the DNA itself. Classically, dense promoter DNA methylation is associated with transcriptional repression.

Gene-Specific Targeting of DNA Methylation in the Mammalian Genome.

DNA methylation is the most widely-studied epigenetic modification, playing a critical role in the regulation of gene expression. Dysregulation of DNA methylation is implicated in the pathogenesis of numerous diseases. For example, aberrant DNA methylation in promoter regions of tumor-suppressor genes has been strongly associated with the development and progression of many different tumors.

Untethered soft robotic matter with passive control of shape morphing and propulsion.

There is growing interest in creating untethered soft robotic matter that can repeatedly shape-morph and self-propel in response to external stimuli. Toward this goal, we printed soft robotic matter composed of liquid crystal elastomer (LCE) bilayers with orthogonal director alignment and different nematic-to-isotropic transition temperatures ( ) to form active hinges that interconnect polymeric tiles. When heated above their respective actuation temperatures, the printed LCE hinges exhibit a large, reversible bending response.

The role of DNA methylation in human trophoblast differentiation.

The placenta is a vital fetal exchange organ connecting mother and baby. Specialised placental epithelial cells, called trophoblasts, are essential for adequate placental function. Trophoblasts transform the maternal vasculature to allow efficient blood flow to the placenta and facilitate adequate nutrient uptake.

Human trophoblasts are primarily distinguished from somatic cells by differences in the pattern rather than the degree of global CpG methylation.

The placenta is a fetal exchange organ connecting mother and baby that facilitates fetal growth DNA methylation is thought to impact placental development and function. Global DNA methylation studies using human placental lysates suggest that the placenta is uniquely hypomethylated compared to somatic tissue lysates, and this hypomethylation is thought to be important in conserving the unique placental gene expression patterns required for successful function. In the placental field, methylation has frequently been examined in tissue lysates, which contain mixed cell types that can confound results.

Germline mutations and somatic inactivation of TRIM28 in Wilms tumour.

Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer.

DNA methylation of hepatic iron sensing genes and the regulation of hepcidin expression.

Production of the iron regulatory peptide hepcidin is tightly controlled by a network of proteins in hepatocytes that sense levels of iron in the circulation (as diferric-transferrin) and in tissues (in ferritin). Human studies show high variability in the normal range of serum hepcidin levels. We have postulated that this may, in part, be related to inter-individual variability in the expression of genes in the iron sensing pathway, potentially governed by epigenetic factors.

Rare case of bilateral traumatic internal carotid artery dissection.

A 55-year-old man was working in a trench when the wall collapsed in on him, pinning him to the wall. On arrival in the emergency department the patient began reporting of right-sided headache. Neurological examination revealed left-sided reduced sensation with weakness.

Putting pontine anatomy into clinical practice: the 16 syndrome.

The anatomical localisation of brainstem syndromes is the domain of the clinical neurologist, though MRI has made an encyclopaedic knowledge of neuroanatomy less crucial. Isolated pontine syndromes comprise ∼20% of the brainstem lacunar syndromes. Typical presentations such as pure motor hemiparesis and ataxic hemiparesis are easily recognisable but atypical syndromes, particularly when bilateral, may present with puzzling signs.

TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells.

Background: Childhood acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments.

Sneddon's syndrome: it is all in the ectoderm.

A 51-year-old man gave a 2-year history of worsening mobility, cognitive decline and headaches. He had a history of thromboembolic stroke, recurrent transient ischaemic attacks and a spontaneous intraventricular haemorrhage. On examination, he had livedo reticularis and perniosis and a systolic murmur.

Genome-wide DNA methylation map of human neutrophils reveals widespread inter-individual epigenetic variation.

The extent of variation in DNA methylation patterns in healthy individuals is not yet well documented. Identification of inter-individual epigenetic variation is important for understanding phenotypic variation and disease susceptibility. Using neutrophils from a cohort of healthy individuals, we generated base-resolution DNA methylation maps to document inter-individual epigenetic variation.