Transcriptome Profiling of Bovine Macrophages Infected by spp. Depicts Foam Cell and Innate Immune Tolerance Phenotypes.

spp. (MAP) is the causative agent of Johne's disease (JD), also known as paratuberculosis, in ruminants. The mechanisms of JD pathogenesis are not fully understood, but it is known that MAP subverts the host immune system by using macrophages as its primary reservoir.

Regulation of platelet-activating factor-induced interleukin-8 expression by protein tyrosine phosphatase 1B.

Background: Platelet-activating factor (PAF) is a potent lipid mediator whose involvement in the onset and progression of atherosclerosis is mediated by, among others, the modulation of cytokine expression patterns. The presence of multiple potential protein-tyrosine phosphatase (PTP) 1B substrates in PAF receptor signaling pathways brought us to investigate its involvement in PAF-induced cytokine expression in monocyte-derived dendritic cells (Mo-DCs) and to study the pathways involved in this modulation.

Methods: We used in-vitro-matured human dendritic cells and the HEK-293 cell line in our studies.

Regulation of platelet-activating factor-mediated protein tyrosine phosphatase 1B activation by a Janus kinase 2/calpain pathway.

Atherosclerosis is a pro-inflammatory condition underlying many cardiovascular diseases. Platelet-activating factor (PAF) and interleukin 6 (IL-6) are actively involved in the onset and progression of atherosclerotic plaques. The involvement of monocyte-derived macrophages is well characterized in the installation of inflammatory conditions in the plaque, but less is known about the contribution of monocyte-derived dendritic cells (Mo-DCs).

Redirecting splicing with bifunctional oligonucleotides.

Ectopic modulators of alternative splicing are important tools to study the function of splice variants and for correcting mis-splicing events that cause human diseases. Such modulators can be bifunctional oligonucleotides made of an antisense portion that determines target specificity, and a non-hybridizing tail that recruits proteins or RNA/protein complexes that affect splice site selection (TOSS and TOES, respectively, for targeted oligonucleotide silencer of splicing and targeted oligonucleotide enhancer of splicing). The use of TOSS and TOES has been restricted to a handful of targets.

Tumor microenvironment-associated modifications of alternative splicing.

Pre-mRNA alternative splicing is modified in cancer, but the origin and specificity of these changes remain unclear. Here, we probed ovarian tumors to identify cancer-associated splicing isoforms and define the mechanism by which splicing is modified in cancer cells. Using high-throughput quantitative PCR, we monitored the expression of splice variants in laser-dissected tissues from ovarian tumors.

Epidural blood patch in a patient with multiple sclerosis: is it safe?

Purpose: Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system resulting in demyelination and axonal injury. Epidural blood patch (EBP) to treat postdural puncture headache (PDPH) in an MS patient may be of concern because of the potential for this to interfere with axonal conduction. Even with normal axons, pressure can interfere with impulse conduction, and it is unknown whether affected axons of the MS patient are particularly vulnerable to the increase in epidural pressure that occurs as a consequence of the EBP.

Lower motor neuron syndrome due to cauda equina hypertrophy with onion bulbs.

Introduction: Hypertrophy of the nerve roots of the cauda equina may occur with both acquired and inherited neuropathies. Although selective nerve root involvement of the sensory roots has been described and termed chronic inflammatory sensory polyradiculoneuropathy (CISP), selective involvement of the proximal motor roots has not been described.

Methods: Clinical, electrophysiological, MRI, and pathological findings are reported.

Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators.

Several apoptotic regulators, including Bcl-x, are alternatively spliced to produce isoforms with opposite functions. We have used an RNA interference strategy to map the regulatory landscape controlling the expression of the Bcl-x splice variants in human cells. Depleting proteins known as core (Y14 and eIF4A3) or auxiliary (RNPS1, Acinus, and SAP18) components of the exon junction complex (EJC) improved the production of the proapoptotic Bcl-x(S) splice variant.

Alternative splicing of SYK regulates mitosis and cell survival.

Most human genes produce multiple mRNA isoforms through alternative splicing. However, the biological relevance of most splice variants remains unclear. In this study, we evaluated the functional impact of alternative splicing in cancer cells.

DOK7 mutations presenting as a proximal myopathy in French Canadians.

DOK7 mutations cause a congenital myasthenic syndrome (OMIM 254300) characterized by a "limb-girdle" phenotype. We identified 7 French-Canadian patients with a previously undiagnosed proximal myopathy. A genome wide scan was performed.

High-throughput quantification of splicing isoforms.

Most human messenger RNAs (mRNAs) are alternatively spliced and many exhibit disease-specific splicing patterns. However, the contribution of most splicing events to the development and maintenance of human diseases remains unclear. As the contribution of alternative splicing events to diagnosis and prognosis is becoming increasingly recognized, it becomes important to develop precise methods to quantify the abundance of these isoforms in clinical samples.

Identification of alternative splicing markers for breast cancer.

Breast cancer is the most common cause of cancer death among women under age 50 years, so it is imperative to identify molecular markers to improve diagnosis and prognosis of this disease. Here, we present a new approach for the identification of breast cancer markers that does not measure gene expression but instead uses the ratio of alternatively spliced mRNAs as its indicator. Using a high-throughput reverse transcription-PCR-based system for splicing annotation, we monitored the alternative splicing profiles of 600 cancer-associated genes in a panel of 21 normal and 26 cancerous breast tissues.

Modulation of 5' splice site selection using tailed oligonucleotides carrying splicing signals.

Background: We previously described the use of tailed oligonucleotides as a means of reprogramming alternative pre-mRNA splicing in vitro and in vivo. The tailed oligonucleotides that were used interfere with splicing because they contain a portion complementary to sequences immediately upstream of the target 5' splice site combined with a non-hybridizing 5' tail carrying binding sites for the hnRNP A1/A2 proteins. In the present study, we have tested the inhibitory activity of RNA oligonucleotides carrying different tail structures.

Small interfering RNA-mediated reduction in heterogeneous nuclear ribonucleoparticule A1/A2 proteins induces apoptosis in human cancer cells but not in normal mortal cell lines.

To prevent their recognition as DNA breaks, the ends of linear chromosomes are organized into telomeres, which are made of proteins bound to telomere-specific, double-stranded repeats and to single-stranded DNA extensions, the G-tails. The mammalian heterogeneous nuclear ribonucleoparticule A1 and A2 proteins can bind with high affinity to such G-tails. Moreover, previous work established that in certain mouse cells a severe reduction in the level of A1 is associated with shortened telomeric repeat tracts, and restoring A1 expression increases telomere length.