Laser Microdissection-Based Protocol for the LC-MS/MS Analysis of the Proteomic Profile of Neuromelanin Granules.

Neuromelanin is a black-brownish pigment, present in so-called neuromelanin granules (NMGs) in dopaminergic neurons of the substantia nigra pars compacta. Besides neuromelanin, NMGs contain a variety of proteins, lipids, and metals. Although NMGs-containing dopaminergic neurons are preferentially lost in neurodegenerative diseases like Parkinson's disease and dementia with Lewy bodies, only little is known about the mechanism of NMG formation and the role of NMGs in health and disease.

CSF Diagnostics: A Potentially Valuable Tool in Neurodegenerative and Inflammatory Disorders Involving Motor Neurons: A Review.

Cerebrospinal fluid (CSF) diagnostics has emerged as a valid tool for a variety of neurological diseases. However, CSF diagnostics has been playing a subordinate role in the diagnosis of many neurological conditions. Thus, in the multitude of neuromuscular diseases in which motor neurons are affected, a CSF sample is rarely taken routinely.

The tobacco carcinogen NNK drives accumulation of DNMT1 at the GR promoter thereby reducing GR expression in untransformed lung fibroblasts.

Small cell lung cancer (SCLC) is a highly aggressive, predominantly cigarette smoke-induced tumour with poor prognosis. The glucocorticoid receptor (GR), a SCLC tumour suppressor gene, is typically reduced in SCLC. We now show that SCLC cells express high levels of DNA methyltransferase 1 (DNMT1) which accumulates at the GR promoter.

Improving HIV proteome annotation: new features of BioAfrica HIV Proteomics Resource.

The Human Immunodeficiency Virus (HIV) is one of the pathogens that cause the greatest global concern, with approximately 35 million people currently infected with HIV. Extensive HIV research has been performed, generating a large amount of HIV and host genomic data. However, no effective vaccine that protects the host from HIV infection is available and HIV is still spreading at an alarming rate, despite effective antiretroviral (ARV) treatment.

Glucocorticoid receptors in lung cancer: new perspectives.

Proper expression of the glucocorticoid receptor (GR) plays an essential role in the development of the lung. GR expression and signalling in the lung is manipulated by administration of synthetic glucocorticoids (Gcs) for the treatment of neonatal, childhood and adult lung diseases. In lung cancers, Gcs are also commonly used as co-treatment during chemotherapy.

The N-terminal transactivation domain of the glucocorticoid receptor mediates apoptosis of human small cell lung cancer cells.

Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis. These cancers are deficient in glucocorticoid receptor (GR) expression, and therefore, resistant to glucocorticoids. Overexpression of the GR both in vivo and in vitro leads to apoptotic cell death suggesting that loss of GR is favorable for cancer growth.

Signals from the lens and Foxc1 regulate the expression of key genes during the onset of corneal endothelial development.

Correct formation of the corneal endothelium is essential for continued development of the anterior segment of the eye. Corneal endothelial development is initiated at E12 when precursor peri-ocular mesenchyme cells migrate into the space between the lens and the presumptive corneal epithelium and begin to respond to signals from the lens, undergoing a mesenchymal to epithelial transition (MET) that is complete by E15.5.

Can stem cells really regenerate the human heart? Use your noggin, dickkopf! Lessons from developmental biology.

The human heart is the first organ to develop and its development is fairly well characterised. In theory, the heart has the capacity to regenerate, as its cardiomyocytes may be capable of cell division and the adult heart contains a cardiac stem cell niche, presumably capable of differentiating into cardiomyocytes and other cardiac-associated cell types. However, as with most other organs, these mechanisms are not activated upon serious injury.

Stem cells - 13 years since their isolation, is there any proven benefit to the patient?

Stem cells are seen as the 'magic bullet'; while this may be true, their efficacy and safety in patients has not yet been established unequivocally. This article summarises the different types of stem cells and gives an overview of their advantages and disadvantages, their use, and potential uses in the patient setting.

Loss of glucocorticoid receptor expression by DNA methylation prevents glucocorticoid induced apoptosis in human small cell lung cancer cells.

Human small cell lung cancer (SCLC) is highly aggressive, and quickly develops resistance to therapy. SCLC cells are typically insensitive to glucocorticoids due to impaired glucocorticoid receptor (GR) expression. This is important as we have previously shown that expression of a GR transgene induces cell death in-vitro, and inhibits tumor growth in-vivo.

Ultradian cortisol pulsatility encodes a distinct, biologically important signal.

Context: Cortisol is released in ultradian pulses. The biological relevance of the resulting fluctuating cortisol concentration has not been explored.

Objective: Determination of the biological consequences of ultradian cortisol pulsatility.

Glucocorticoid receptor over-expression promotes human small cell lung cancer apoptosis in vivo and thereby slows tumor growth.

Small cell lung cancer (SCLC) is an aggressive tumor, associated with ectopic ACTH syndrome. We have shown that SCLC cells are glucocorticoid receptor (GR) deficient, and that restoration of GR expression confers glucocorticoid sensitivity and induces apoptosis in vitro. To determine the effects of GR expression in vivo, we characterized a mouse SCLC xenograft model that secretes ACTH precursor peptides, and so drives high circulating corticosterone concentrations (analogous to the ectopic ACTH syndrome).

Novel therapeutic agents targeting the glucocorticoid receptor for inflammation and cancer.

Glucocorticoids, through their interaction with the ubiquitous glucocorticoid receptor (GR), have extensive and disparate effects on different cells and tissues. They have long been used in the treatment of asthma, arthritis and autoimmune diseases based on their anti-inflammatory and immunosuppressive effects. For these reasons, as well as for their ability to induce massive apoptosis in hematological malignancies, they are also commonly used as cotreatment in cancers.

Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor.

Glucocorticoid (GC) receptors (GRs) have profound anti-survival effects on human small cell lung cancer (SCLC). To explore the basis of these effects, protein partners for GRs were sought using a yeast two-hybrid screen. We discovered a novel gene, FAM33A, subsequently identified as a SKA1 partner and involved in mitosis, and so renamed Ska2.

Identification of Tgf beta1i4 as a downstream target of Foxc1.

Craniofacial development is severely affected by null mutations in Foxc1, indicating a multifunctional role for Foxc1 in ocular, maxilla and mandible, skull and facial gland development. To delineate signaling pathways in which Foxc1 is involved we compared the transcriptomes of whole heads of Foxc1+/+ and Foxc1-/- embryos using a candidate cDNA array comprising genes expressed in the head mesenchyme and ocular region, and a 7K oligo array. Absence of Foxc1 led to downregulation of Stat1 and Galnt4, and upregulation of Tgf beta1i4 at embryonic day 13.

The role of the forkhead transcription factor, Foxc1, in the development of the mouse lacrimal gland.

The lacrimal gland produces secretions that lubricate and protect the cornea of the eye. Foxc1 encodes a forkhead/winged helix transcription factor required for the development of many embryonic organs. Autosomal dominant mutations in human FOXC1 cause eye disorders such as Axenfeld-Rieger Syndrome and glaucoma iris hypoplasia, resulting from malformation of the anterior segment of the eye.