MedWorm: Biomedical Science Top 20

LRRK2 and Human Disease: A Complicated Question or a Question of Complexes?

Science Signaling — Sun, 22 Jan 2012 17:18:02 +0100

Authors: Lewis PA, Manzoni C Abstract Leucine-rich repeat kinase 2 (LRRK2) is linked to various diseases, including Parkinson's disease, cancer, and leprosy. Data from LRRK2 knockout mice has highlighted a possible role for LRRK2 in regulating signaling pathways that are linked to the pathogenesis of Crohn's disease. Here, we examine how LRRK2's role as a signaling hub in the cell could lead to diverse pathologies. PMID: 22253261 [PubMed - in process] (Source: Science Signaling)

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Cardiovascular Development

Springer Biomedical Sciences titles — Mon, 09 Jan 2012 22:35:57 +0100

Methods and Protocolsseries:Methods in Molecular BiologyCongenital heart disease is the leading cause of infant death and affects approximately one in every 100 babies born in the United States. The study of cardiovascular development has acquired new momentum in last twenty years due to the advancement of modern molecular biology and new available equipments and techniques. In Cardiovascular Development: Methods and Protocols expert researchers in ... (Source: Springer Biomedical Sciences titles)

The {alpha}v{beta}6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells

Journal of Clinical Investigation — Mon, 09 Jan 2012 22:32:58 +0100

Allergic asthma is the most common form of asthma, affecting more than 10 million Americans. Although it is clear that mast cells have a key role in the pathogenesis of allergic asthma, the mechanisms by which they regulate airway narrowing in vivo remain to be elucidated. Here we report that mice lacking αvβ6 integrin are protected from exaggerated airway narrowing in a model of allergic asthma. Expression microarrays of the airway epithelium revealed mast cell proteases among the most prominent differentially expressed genes, with expression of mouse mast cell protease 1 (mMCP-1) induced by allergen challenge in WT mice and expression of mMCP-4, -5, and -6 increased at baseline in β6-deficient mice. These findings were most likely explained by loss of TGF-β...

Heparan sulfate sulfatase SULF2 regulates PDGFR{alpha} signaling and growth in human and mouse malignant glioma

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

In this study, we demonstrated that the extracellular sulfatase, SULF2, an enzyme that regulates multiple HSPG-dependent RTK signaling pathways, was expressed in primary human GBM tumors and cell lines. Knockdown of SULF2 in human GBM cell lines and generation of gliomas from Sulf2–/– tumorigenic neurospheres resulted in decreased growth in vivo in mice. We found a striking SULF2 dependence in activity of PDGFRα, a major signaling pathway in GBM. Ablation of SULF2 resulted in decreased PDGFRα phosphorylation and decreased downstream MAPK signaling activity. Interestingly, in a survey of SULF2 levels in different subtypes of GBM, the proneural subtype, characterized by aberrations in PDGFRα, demonstrated the strongest SULF2 expression. Therefore, in a...

T-rays technology could help develop Star Trek-style hand-held medical scanners

Imperial College News — Fri, 20 Jan 2012 05:00:00 +0100

Scientists have developed a new way to create Terahertz waves (T-rays) that may one day lead to biomedical detective devices similar to the 'tricorder' scanner used in Star Trek - News release (Source: Imperial College News)

Direct and efficient cellular transformation of primary rat mesenchymal precursor cells by KSHV

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

Infections by viruses are associated with approximately 12% of human cancer. Kaposi’s sarcoma-associated herpesvirus (KSHV) is causally linked to several malignancies commonly found in AIDS patients. The mechanism of KSHV-induced oncogenesis remains elusive, due in part to the lack of an adequate experimental system for cellular transformation of primary cells. Here, we report efficient infection and cellular transformation of primary rat embryonic metanephric mesenchymal precursor cells (MM cells) by KSHV. Cellular transformation occurred at as early as day 4 after infection and in nearly all infected cells. Transformed cells expressed hallmark vascular endothelial, lymphatic endothelial, and mesenchymal markers and efficiently induced tumors in nude mice. KSHV established latent ...

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Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

Journal of Clinical Investigation — Tue, 24 Jan 2012 19:12:02 +0100

Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor...

Wnt/β-Catenin Signaling and AXIN1 Regulate Apoptosis Triggered by Inhibition of the Mutant Kinase BRAFV600E in Human Melanoma.

Science Signaling — Sun, 22 Jan 2012 17:18:02 +0100

Authors: Biechele TL, Kulikauskas RM, Toroni RA, Lucero OM, Swift RD, James RG, Robin NC, Dawson DW, Moon RT, Chien AJ Abstract Because the Wnt/β-catenin signaling pathway is linked to melanoma pathogenesis and to patient survival, we conducted a kinome small interfering RNA (siRNA) screen in melanoma cells to expand our understanding of the kinases that regulate this pathway. We found that BRAF signaling, which is constitutively activated in many melanomas by the BRAF(V600E) mutation, inhibits Wnt/β-catenin signaling in human melanoma cells. Because inhibitors of BRAF(V600E) show promise in ongoing clinical trials, we investigated whether altering Wnt/β-catenin signaling might enhance the efficacy of the BRAF(V600E) inhibitor PLX4720. We found that endogenous β-catenin was req...

Oxygen Transport to Tissue XXXIII

Springer Biomedical Sciences titles — Fri, 27 Jan 2012 17:52:30 +0100

series:Advances in Experimental Medicine and BiologyBased on the 38th annual conference of the International Society on Oxygen Transport to Tissue (ISOTT), held in Ascona, Switzerland in July 2010, this volume covers all aspects of oxygen transport from air to the cells, organs and organisms; instrumentation and methods to sense oxygen and clinical evidence. It covers near infrared spectroscopy, brain oxygenation, tumor biology, angiogenesis ... (Source: Springer Biomedical Sciences titles)

Skin tissue generation by laser cell printing

Biotechnology and Bioengineering — Fri, 27 Jan 2012 18:56:31 +0100

AbstractFor the aim of ex vivo engineering of functional tissue substitutes, Laser‐assisted BioPrinting (LaBP) is under investigation for the arrangement of living cells in predefined patterns. So far three‐dimensional arrangements of single or two‐dimensional patterning of different cell types have been presented. It has been shown that cells are not harmed by the printing procedure. We now demonstrate for the first time the 3D arrangement of vital cells by LaBP as multicellular grafts analogous to native archetype and the formation of tissue by these cells.For this purpose, fibroblasts and keratinocytes embedded in collagen were printed in 3D as a simple example for skin tissue. To study cell functions and tissue formation process in 3D, different characteristics such as cell local...

Title page/Editorial Board

Medical Hypotheses — Fri, 03 Feb 2012 18:55:56 +0100

(Source: Medical Hypotheses)

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Trauma Fact Sheet

NIGMS - What's New — Mon, 30 Jan 2012 15:57:45 +0100

(Source: NIGMS - What's New)

Yes, even human brown fat is on fire!

Journal of Clinical Investigation — Tue, 24 Jan 2012 19:12:02 +0100

That adult humans possess brown fat is now accepted — but is the brown fat metabolically active? Does human brown fat actually combust fat to release heat? In this issue of the JCI, Ouellet et al. demonstrate that metabolism in brown fat really is increased when adult humans are exposed to cold. This boosts the possibility that calorie combustion in brown fat may be of significance for our metabolism and, correspondingly, that the absence of brown fat may increase our proneness to obesity — provided that brown fat becomes activated not only by cold but also through food-related stimuli. (Source: Journal of Clinical Investigation)

Focus Issue: Wnt and β-Catenin Signaling in Development and Disease.

Science Signaling — Sun, 22 Jan 2012 17:18:02 +0100

Authors: Gough NR Abstract The Wnt pathways represent key signaling networks involved in development, both in tissue specification and in cellular migration. Wnt signaling also plays key roles in tissue homeostasis in adult animals, and aberrant Wnt signaling is associated with several forms of cancer. This issue includes descriptions of a proapoptotic function for Wnt signaling in melanoma, an interplay between Wnt and bone morphogenetic proteins in tooth organogenesis, and a noncanonical role for Wnt in neuronal guidance. PMID: 22234609 [PubMed - in process] (Source: Science Signaling)

Editorial Board

Metabolism - Clinical and Experimental — Tue, 24 Jan 2012 19:16:00 +0100

(Source: Metabolism - Clinical and Experimental)

The Biology of Subcellular Nitric Oxide(Rőszer)

Springer Biomedical Sciences titles — Sun, 15 Jan 2012 06:32:03 +0100

(Source: Springer Biomedical Sciences titles)

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MicroRNAs, fibrotic remodeling, and aortic aneurysms

Journal of Clinical Investigation — Tue, 24 Jan 2012 19:12:02 +0100

This study highlights the relevance of miR-29b in aortic disease but also raises questions about its specific role. (Source: Journal of Clinical Investigation)

A wnt-bmp feedback circuit controls intertissue signaling dynamics in tooth organogenesis.

Science Signaling — Sun, 22 Jan 2012 17:18:02 +0100

Authors: O'Connell DJ, Ho JW, Mammoto T, Turbe-Doan A, O'Connell JT, Haseley PS, Koo S, Kamiya N, Ingber DE, Park PJ, Maas RL Abstract Many vertebrate organs form through the sequential and reciprocal exchange of signaling molecules between juxtaposed epithelial and mesenchymal tissues. We undertook a systems biology approach that combined the generation and analysis of large-scale spatiotemporal gene expression data with mouse genetic experiments to gain insight into the mechanisms that control epithelial-mesenchymal signaling interactions in the developing mouse molar tooth. We showed that the shift in instructive signaling potential from dental epithelium to dental mesenchyme was accompanied by temporally coordinated genome-wide changes in gene expression in both compartments. T...

Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development

Journal of Clinical Investigation — Tue, 24 Jan 2012 19:12:02 +0100

MicroRNAs (miRs) regulate gene expression at the posttranscriptional level and play crucial roles in vascular integrity. As such, they may have a role in modifying abdominal aortic aneurysm (AAA) expansion, the pathophysiological mechanisms of which remain incompletely explored. Here, we investigate the role of miRs in 2 murine models of experimental AAA: the porcine pancreatic elastase (PPE) infusion model in C57BL/6 mice and the AngII infusion model in Apoe–/– mice. AAA development was accompanied by decreased aortic expression of miR-29b, along with increased expression of known miR-29b targets, Col1a1, Col3a1, Col5a1, and Eln, in both models. In vivo administration of locked nucleic acid anti–miR-29b greatly increased collagen expression, leading to an early fib...

Vaccines for Pandemic Influenza

Springer Biomedical Sciences titles — Wed, 28 Dec 2011 12:07:00 +0100

series:Current Topics in Microbiology and ImmunologyRecent years have seen unprecedented outbreaks of avian influenza A viruses. In particular, highly pathogenic H5N1 viruses have not only resulted in widespread outbreaks in domestic poultry, but have been transmitted to humans resulting in numerous fatalities. The rapid expansion in their geographic distribution and the possibility that these viruses could acquire the ability to spread from ... (Source: Springer Biomedical Sciences titles)