Lack of evidence for a genetic association between FGF20 and Parkinson's disease in Finnish and Greek patients

BACKGROUND: Fibroblast growth factor 20 (FGF20) is a neurotrophic factor preferentially expressed in the substantia nigra of rat brain and could be involved in dopaminergic neurons survival. Recently, a strong genetic association has been found between FGF20 gene and the risk of suffering from Parkinson's disease (PD). Our aim was to replicate this association in two independent populations. METHODS: Allelic, genotypic, and haplotype frequencies of four biallelic polymorphisms were assessed in 151 sporadic PD cases and 186 controls from Greece, and 144 sporadic PD patients and 135 controls from Finland. RESULTS: No association was found in any of the populations studied. CONCLUSION: Taken together, these findings suggest that common genetic variants in FGF20 are not a risk factor for PD in, at least, some European populations

Carcinoma Arising from Brunner's Gland in the Duodenum after 17 Years of Observation – A Case Report and Literature Review

A 60-year-old man presented with melena and hematemesis in 1984. Esophagogastroduodenoscopy (EGD) detected a small protruding lesion in the duodenal bulb, which was diagnosed as Brunner's adenoma. No significant change was detected in subsequent annual EGD and biopsies for 10 years, after which the patient was not observed for 7 years. The patient presented with melena again in 2001. The lesion had changed shape to become a 10 mm sessile tumor with a central depression, and following a biopsy was diagnosed as an adenocarcinoma. The patient underwent partial resection of the duodenum. Histopathological assessment showed acidophilic cells with swollen nuclei, and clear cells forming a tubular or papillary tubule in the mucosal lamina propria and submucosal layer. The tumor cells stained positive for lysozyme, indicating that they arose from Brunner's gland. The patient showed no sign of recurrence and was disease-free for more than 34 months after surgery. The patient died of pneumonia. This is an extremely rare case of primary duodenal carcinoma arising from Brunner's gland in a patient observed for 17 years

Age- and calorie-independent life span extension from dietary restriction by bacterial deprivation in Caenorhabditis elegans

Background: Dietary restriction (DR) increases life span and delays age-associated disease in many organisms. The mechanism by which DR enhances longevity is not well understood. Results: Using bacterial food deprivation as a means of DR in C. elegans, we show that transient DR confers long-term benefits including stress resistance and increased longevity. Consistent with studies in the fruit fly and in mice, we demonstrate that DR also enhances survival when initiated late in life. DR by bacterial food deprivation significantly increases life span in worms when initiated as late as 24 days of adulthood, an age at which greater than 50% of the cohort have died. These survival benefits are, at least partially, independent of food consumption, as control fed animals are no longer consuming bacterial food at this advanced age. Animals separated from the bacterial lawn by a barrier of solid agar have a life span intermediate between control fed and food restricted animals. Thus, we find that life span extension from bacterial deprivation can be partially suppressed by a diffusible component of the bacterial food source, suggesting a calorie-independent mechanism for life span extension by dietary restriction. Conclusion: Based on these findings, we propose that dietary restriction by bacterial deprivation increases longevity in C. elegans by a combination of reduced food consumption and decreased food sensing

FGF-2 Deficiency Does Not Influence FGF Ligand and Receptor Expression during Development of the Nigrostriatal System

Secreted proteins of the fibroblast growth factor (FGF) family play important roles during development of various organ systems. A detailed knowledge of their temporal and spatial expression profiles, especially of closely related FGF family members, are essential to further identification of specific functions in distinct tissues. In the central nervous system dopaminergic neurons of the substantia nigra and their axonal projections into the striatum progressively degenerate in Parkinson's disease. In contrast, FGF-2 deficient mice display increased numbers of dopaminergic neurons. In this study, we determined the expression profiles of all 22 FGF-ligands and 10 FGF-receptor isoforms, in order to clarify, if FGF-2 deficiency leads to compensatory up-regulation of other FGFs in the nigrostriatal system. Three tissues, ventral mesencephalon (VM), striatum (STR) and as reference tissue spinal cord (SC) of wild-type and FGF-2 deficient mice at four developmental stages E14.5, P0, P28, and adult were comparatively analyzed by quantitative RT-PCR. As no differences between the genotypes were observed, a compensatory up-regulation can be excluded. Moreover, this analysis revealed that the majority of FGF-ligands (18/22) and FGF-receptors (9/10) are expressed during normal development of the nigrostriatal system and identified dynamic changes for some family members. By comparing relative expression level changes to SC reference tissue, general alterations in all 3 tissues, such as increased expression of FGF-1, -2, -22, FgfR-2c, -3c and decreased expression of FGF-13 during postnatal development were identified. Further, specific changes affecting only one tissue, such as increased FGF-16 (STR) or decreased FGF-17 (VM) expression, or two tissues, such as decreased expression of FGF-8 (VM, STR) and FGF-15 (SC, VM) were found. Moreover, 3 developmentally down-regulated FGFs (FGF-8b, FGF-15, FGF-17a) were functionally characterized by plasmid-based over-expression in dissociated E11.5 VM cell cultures, however, such a continuous exposure had no influence on the yield of dopaminergic neurons in vitro

The HLH-6 Transcription Factor Regulates C. elegans Pharyngeal Gland Development and Function

The Caenorhabditis elegans pharynx (or foregut) functions as a pump that draws in food (bacteria) from the environment. While the “organ identity factor” PHA-4 is critical for formation of the C. elegans pharynx as a whole, little is known about the specification of distinct cell types within the pharynx. Here, we use a combination of bioinformatics, molecular biology, and genetics to identify a helix-loop-helix transcription factor (HLH-6) as a critical regulator of pharyngeal gland development. HLH-6 is required for expression of a number of gland-specific genes, acting through a discrete cis-regulatory element named PGM1 (Pharyngeal Gland Motif 1). hlh-6 mutants exhibit a frequent loss of a subset of glands, while the remaining glands have impaired activity, indicating a role for hlh-6 in both gland development and function. Interestingly, hlh-6 mutants are also feeding defective, ascribing a biological function for the glands. Pharyngeal pumping in hlh-6 mutants is normal, but hlh-6 mutants lack expression of a class of mucin-related proteins that are normally secreted by pharyngeal glands and line the pharyngeal cuticle. An interesting possibility is that one function of pharyngeal glands is to secrete a pharyngeal lining that ensures efficient transport of food along the pharyngeal lumen

Monitoring the orientation of rare-earth-doped nanorods for flow shear tomography

Rare-earth phosphors exhibit unique luminescence polarization features originating from the anisotropic symmetry of the emitter ion's chemical environment. However, to take advantage of this peculiar property, it is necessary to control and measure the ensemble orientation of the host particles with a high degree of precision. Here, we show a methodology to obtain the photoluminescence polarization of Eu-doped LaPO4 nano rods assembled in an electrically modulated liquid-crystalline phase. We measure Eu3+ emission spectra for the three main optimal configurations ({\sigma}, {\pi} and {\alpha}, depending on the direction of observation and the polarization axes) and use them as a reference for the nano rod orientation analysis. Based on the fact that flowing nano rods tend to orient along the shear strain profile, we use this orientation analysis to measure the local shear rate in a flowing liquid. The potential of this approach is then demonstrated through tomographic imaging of the shear rate distribution in a microfluidic system.Comment: 8 pages, 3 figures + supplementary files for experimental and numerical method

β2microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients

Colorectal cancer (CRC) is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. One of the most important determinants of CRC survival is lymph node metastasis. To determine whether molecular markers might be prognostic for lymph node metastases, we measured by quantitative real-time RT–PCR the expression levels of 15 cancer-associated genes in formalin-fixed paraffin-embedded primary tissues derived from stage I–IV CRC patients with (n=20) and without (n=18) nodal metastases. Using the mean of the 15 genes as an internal reference control, we observed that low expression of β2microglobulin (B2M) was a strong prognostic indicator of lymph node metastases (area under the curve (AUC)=0.85; 95% confidence interval (CI)=0.69–0.94). We also observed that the expression ratio of B2M/Spint2 had the highest prognostic accuracy (AUC=0.87; 95% CI=0.71–0.96) of all potential two-gene combinations. Expression values of Spint2 correlated with the mean of the entire gene set at an R2 value of 0.97, providing evidence that Spint2 serves not as an independent prognostic gene, but rather as a reliable reference control gene. These studies are the first to demonstrate a prognostic role of B2M at the mRNA level and suggest that low B2M expression levels might be useful for identifying patients with lymph node metastasis and/or poor survival