Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
2,699
result(s) for
"Lu, Richard"
Sort by:
The Beatles in comics
\"In ten years of existence and only eight years of recording history, John Lennon, Paul McCartney, George Harrison and Ringo Starr recorded twelve albums, composed more than 200 songs and revolutionized the world of music. Hundreds of books have explored this mythical group but The Beatles in Comics proposes an altogether different discovery. Through this volume, you'll be able to relive their greatest successes but also discover often overlooked anecdotes. From the Quarrymen to the split-up, through Beatlemania, here's the story of the Beatles told in a new light, through comics and fascinating fact-filled chapters.\"--Page 4 of cover.
Book
SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia
SLIT2 is a secreted polypeptide that guides migration of cells expressing Roundabout 1 and 2 (ROBO1 and ROBO2) receptors. Herein, we investigated SLIT2/ROBO signaling effects in gliomas. In patients with glioblastoma (GBM), SLIT2 expression increased with malignant progression and correlated with poor survival and immunosuppression. Knockdown of SLIT2 in mouse glioma cells and patient-derived GBM xenografts reduced tumor growth and rendered tumors sensitive to immunotherapy. Tumor cell SLIT2 knockdown inhibited macrophage invasion and promoted a cytotoxic gene expression profile, which improved tumor vessel function and enhanced efficacy of chemotherapy and immunotherapy. Mechanistically, SLIT2 promoted microglia/macrophage chemotaxis and tumor-supportive polarization via ROBO1- and ROBO2-mediated PI3K-γ activation. Macrophage Robo1 and Robo2 deletion and systemic SLIT2 trap delivery mimicked SLIT2 knockdown effects on tumor growth and the tumor microenvironment (TME), revealing SLIT2 signaling through macrophage ROBOs as a potentially novel regulator of the GBM microenvironment and immunotherapeutic target for brain tumors.
Journal Article
Ten-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain
Ten-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation of
Tet1
results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lacking
Tet1
in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and 5-hydroxymethylcytosine (5hmC) profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport.
Tet1
-deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene,
Itpr2
, impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice.
Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelination during development and remyelination in mice.
Journal Article
Epigenetic regulation of oligodendrocyte myelination in developmental disorders and neurodegenerative diseases version 1; peer review: 2 approved
Oligodendrocytes are the critical cell types giving rise to the myelin nerve sheath enabling efficient nerve transmission in the central nervous system (CNS). Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are maintained throughout life. Deficits in the generation, proliferation, or differentiation of these cells or their maintenance have been linked to neurological disorders ranging from developmental disorders to neurodegenerative diseases and limit repair after CNS injury. Understanding the regulation of these processes is critical for achieving proper myelination during development, preventing disease, or recovering from injury. Many of the key factors underlying these processes are epigenetic regulators that enable the fine tuning or reprogramming of gene expression during development and regeneration in response to changes in the local microenvironment. These include chromatin remodelers, histone-modifying enzymes, covalent modifiers of DNA methylation, and RNA modification-mediated mechanisms. In this review, we will discuss the key components in each of these classes which are responsible for generating and maintaining oligodendrocyte myelination as well as potential targeted approaches to stimulate the regenerative program in developmental disorders and neurodegenerative diseases.
Journal Article
Pitfalls and complications of enhanced-view totally extraperitoneal approach to abdominal wall reconstruction
BackgroundThe enhanced-view totally extraperitoneal access technique (eTEP) to minimally invasive retromuscular abdominal wall reconstruction is a relatively novel technique that has continued to gain popularity. There is a paucity of information regarding the prevention and management of eTEP complications. We reviewed the literature to evaluate the complications reported with eTEP ventral hernia repair and discuss the main complications associated with this technique.MethodsA literature search via PubMed was performed focusing on eTEP ventral hernia repair. Based on the available literature and own practice experience, the authors discuss key strategies for preventing and managing complications associated with the eTEP approach.ResultsOne hundred fifty studies were identified. Forty-seven studies were fully reviewed and twenty-four were included in this review. The technical details of the technique were described as performed by the authors. Postoperative complications were classified into different categories and discussed separately.ConclusionAs the eTEP approach continues to gain popularity, it is essential to consider its unique complications. A focus on prevention with anatomical bearings and sound surgical technique is paramount.
Journal Article
CTCF-mediated chromatin looping in EGR2 regulation and SUZ12 recruitment critical for peripheral myelination and repair
Chromatin organization is critical for cell growth, differentiation, and disease development, however, its functions in peripheral myelination and myelin repair remain elusive. In this report, we demonstrate that the CCCTC-binding factor (CTCF), a crucial chromatin organizer, is essential for Schwann cell myelination and myelin regeneration after nerve injury. Inhibition of CTCF or its deletion blocks Schwann cell differentiation at the pro-myelinating stage, whereas overexpression of CTCF promotes the myelination program. We find that CTCF establishes chromatin interaction loops between enhancer and promoter regulatory elements and promotes expression of a key pro-myelinogenic factor EGR2. In addition, CTCF interacts with SUZ12, a component of polycomb-repressive-complex 2 (PRC2), to repress the transcriptional program associated with negative regulation of Schwann cell maturation. Together, our findings reveal a dual role of CTCF-dependent chromatin organization in promoting myelinogenic programs and recruiting chromatin-repressive complexes to block Schwann cell differentiation inhibitors to control peripheral myelination and repair.
Myelination by Schwann cells (SC) in the peripheral nervous system is essential for motor function, and dysregulation of SC myelination can lead to various neuropathies. Here the authors describe a critical role of CCCTC-binding factor (CTCF)-dependent chromatin reorganization in peripheral myelination and myelin regeneration after injury.
Journal Article
Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8
Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming, implicating chromatin remodeling. Mounting evidence indicates that chromatin remodelers play important roles during normal development and their mutations are associated with neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE syndrome and CHD8 being one of the strongest autism spectrum disorder (ASD) high-risk–associated genes. Herein, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin binding profile, combined with transcriptome and chromatin accessibility analyses of Chd7-deleted OPCs, demonstrates that Chd7 protects nonproliferative OPCs from apoptosis by chromatin closing and transcriptional repression of p53. Furthermore, Chd7 controls OPC differentiation through chromatin opening and transcriptional activation of key regulators, including Sox10, Nkx2.2, and Gpr17. However, Chd7 is dispensable for oligodendrocyte stage progression, consistent with Chd8 compensatory function, as suggested by their common chromatin-binding profiles and genetic interaction. Finally, CHD7 and CHD8 bind in OPCs to a majority of ASD risk-associated genes, suggesting an implication of oligodendrocyte lineage cells in ASD neurological defects. Our results thus offer new avenues to understand and modulate the CHD7 and CHD8 functions in normal development and disease.
Journal Article
STAT3 dictates β-cell apoptosis by modulating PTEN in streptozocin-induced hyperglycemia
Insufficient pancreatic β-cell mass or insulin-producing β-cells are implicated in all forms of diabetes mellitus. However, the molecular mechanisms underlying β-cell destruction are complex and not fully defined. Here we observed that activation of STAT3 is intensely and specifically inhibited in β-cells under hyperglycemic conditions. By knocking out STAT3 specifically in mouse β-cells, we found that the loss of STAT3 sensitized mice to three low doses of STZ stimulation resulting in hyperglycemia. Mechanistically, accumulating PTEN, induced by STAT3 deficiency, directly represses phosphorylation of AKT, which negatively modulates transcription factor activation, dysregulates β-cell function, positively promotes apoptotic signaling, and finally induces β-cell apoptosis. Notably, the defective secretion of insulin and β-cells apoptosis was completely rescued by PTEN ablation in STAT3-null islets or PTEN inhibitor bpv(phen) treatment. Thus our data suggest that STAT3 is a vital modulator of β-cell survival and function, highlighting a critical role for STAT3 in the negative regulation of PTEN-AKT signaling pathway associated with β-cell dysfunction and apoptosis.
Journal Article
PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism
Glioblastoma (GBM) is the most common and aggressive primary brain tumor, but the mechanisms underlying tumor growth and progression remain unclear. The protein arginine methyltransferases (PRMTs) regulate a variety of biological processes, however, their roles in GBM growth and progression are not fully understood. In this study, our functional analysis of gene expression networks revealed that among the PRMT family expression of PRMT3 was most significantly enriched in both GBM and low-grade gliomas. Higher PRMT3 expression predicted poorer overall survival rate in patients with gliomas. Knockdown of PRMT3 markedly reduced the proliferation and migration of GBM cell lines and patient-derived glioblastoma stem cells (GSC) in cell culture, while its over-expression increased the proliferative capacity of GSC cells by promoting cell cycle progression. Consistently, stable PRMT3 knockdown strongly inhibited tumor growth in xenograft mouse models, along with a significant decrease in cell proliferation as well as an increase in apoptosis. We further found that PRMT3 reprogrammed metabolic pathways to promote GSC growth via increasing glycolysis and its critical transcriptional regulator HIF1α. In addition, pharmacological inhibition of PRMT3 with a PRMT3-specific inhibitor SGC707 impaired the growth of GBM cells. Thus, our study demonstrates that PRMT3 promotes GBM progression by enhancing HIF1A-mediated glycolysis and metabolic rewiring, presenting a point of metabolic vulnerability for therapeutic targeting in malignant gliomas.
Journal Article
Dual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation
Constitutive activation of Wnt/β-catenin inhibits oligodendrocyte myelination. Tcf7l2/Tcf4, a β-catenin transcriptional partner, is required for oligodendrocyte differentiation. How Tcf7l2 modifies β-catenin signalling and controls myelination remains elusive. Here we define a stage-specific Tcf7l2-regulated transcriptional circuitry in initiating and sustaining oligodendrocyte differentiation. Multistage genome occupancy analyses reveal that Tcf7l2 serially cooperates with distinct co-regulators to control oligodendrocyte lineage progression. At the differentiation onset, Tcf7l2 interacts with a transcriptional co-repressor Kaiso/Zbtb33 to block β-catenin signalling. During oligodendrocyte maturation, Tcf7l2 recruits and cooperates with Sox10 to promote myelination. In that context, Tcf7l2 directly activates cholesterol biosynthesis genes and cholesterol supplementation partially rescues oligodendrocyte differentiation defects in
Tcf712
mutants. Together, we identify stage-specific co-regulators Kaiso and Sox10 that sequentially interact with Tcf7l2 to coordinate the switch at the transitions of differentiation initiation and maturation during oligodendrocyte development, and point to a previously unrecognized role of Tcf7l2 in control of cholesterol biosynthesis for CNS myelinogenesis.
Wnt/β-catenin signaling regulates oligodendrocyte (OL) development. Here the authors show that Tcf7l2, a β-catenin transcriptional partner,sequentially interacts with stage-specific partners to coordinate the transitions of differentiation initiation and maturation during OL development.
Journal Article