Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies

miR-124-1 is a tumour suppressor microRNA (miR). Epigenetic deregulation of miRs is implicated in carcinogenesis. Promoter DNA methylation and histone modification of miR-124-1 was studied in 5 normal marrow controls, 4 lymphoma, 8 multiple myeloma (MM) cell lines, 230 diagnostic primary samples of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), MM, and non-Hodgkin's lymphoma (NHL), and 53 MM samples at stable disease or relapse. Promoter of miR-124-1 was unmethylated in normal controls but homozygously methylated in 4 of 4 lymphoma and 4 of 8 myeloma cell lines. Treatment of 5-Aza-2′-deoxycytidine led to miR-124-1 demethylation and re-expression of mature miR-124, which also associated with emergence of euchromatic trimethyl H3K4 and consequent downregulation of CDK6 in myeloma cells harboring homozygous miR-124-1 methylation. In primary samples at diagnosis, miR-124-1 methylation was absent in CML but detected in 2% each of MM at diagnosis and relapse/progression, 5% ALL, 15% AML, 14% CLL and 58.1% of NHL (p<0.001). Amongst lymphoid malignancies, miR-124-1 was preferentially methylated in NHL than MM, CLL or ALL. In primary lymphoma samples, miR-124-1 was preferentially hypermethylated in B- or NK/T-cell lymphomas and associated with reduced miR-124 expression. In conclusion, miR-124-1 was hypermethylated in a tumour-specific manner, with a heterochromatic histone configuration. Hypomethylation led to partial restoration of euchromatic histone code and miR re-expression. Infrequent miR-124-1 methylation detected in diagnostic and relapse MM samples showed an unimportant role in MM pathogenesis, despite frequent methylation found in cell lines. Amongst haematological cancers, miR-124-1 was more frequently hypermethylated in NHL, and hence warrants further study

LGen - A Lattice-Based Candidate Set Generation Algorithm for I/O Efficient Association Rule Mining

Most algorithms for association rule mining are variants of the basic Apriori algorithm [1]. One characteristic of these Apriori-based algorithms is that candidate itemsets are generated in rounds, with the size of the itemsets incremented by one per round. The number of database scans required by Apriori-based algorithms thus depends on the size of the largest large itemsets. In this paper we devise a more general candidate set generation algorithm, LGen, which generates candidate itemsets of multiple sizes during each database scan. We show that, given a reasonable set of suggested large itemsets, LGen can significantly reduce the number of I/O passes required. In the best cases, only two passes are sufficient to discover all the large itemsets irrespective of the size of the largest ones. Keywords: Data mining, association rules, lattice, Apriori, LGen 1 Introduction Data mining has recently attracted considerable attention from database practitioners and researchers beca..

Hepatic Actinomycosis Presenting as a Liver Tumour: Case Report and Literature Review

Hepatic actinomycosis poses a difficult problem in both diagnosis and management. We report the management of a patient with isolated hepatic actinomycosis, and review the clinical features and management of patients with hepatic actinomycosis mimicking liver tumour

Mask-inspired moisture-transmitting and durable thermochromic perovskite smart windows

Abstract Thermochromic perovskite smart windows (TPWs) are a cutting-edge energy-efficient window technology. However, like most perovskite-based devices, humidity-related degradation limits their widespread application. Herein, inspired by the structure of medical masks, a unique triple-layer thermochromic perovskite window (MTPW) that enable sufficient water vapor transmission to trigger the thermochromism but effectively repel detrimental water and moisture to extend its lifespan is developed. The MTPW demonstrates superhydrophobicity and maintains a solar modulation ability above 20% during a 45-day aging test, with a decay rate 37 times lower than that of a pristine TPW. It can also immobilize lead ions and significantly reduce lead leakage by 66 times. Furthermore, a significant haze reduction from 90% to 30% is achieved, overcoming the blurriness problem of TPWs. Benefiting from the improved optical performance, extended lifespan, suppressed lead leakage, and facile fabrication, the MTPW pushes forward the wide applications of smart windows in green buildings

MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells.

Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remain elusive. In this study, we show that microRNAs are differentially expressed during RGC development and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of phosphatase and tensin homolog (PTEN), a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors. This study uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and it demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity in optic neuropathies

MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells.

Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remain elusive. In this study, we show that microRNAs are differentially expressed during RGC development and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of phosphatase and tensin homolog (PTEN), a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors. This study uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and it demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity in optic neuropathies