Unusual presentation of choriocarcinoma

Background  

Choriocarcinoma is an aggressive neoplasm arising in the body of the uterus. The disease normally spreads to lung and brain.     

Differential expression level of cytokeratin 8 in cells of the bovine nucleus pulposus complicates the search for specific intervertebral disc cell markers

Introduction  

Development of cell therapies for repairing the intervertebral disc is limited by the lack of a source of healthy human disc cells. Stem cells, particularly mesenchymal stem cells, are seen as a potential source but differentiation strategies are limited by the lack of specific markers that can distinguish disc cells from articular chondrocytes.     

C. elegans pharyngeal morphogenesis requires both de novo synthesis of pyrimidines and synthesis of heparan sulfate proteoglycans

The C. elegans pharynx undergoes elongation and morphogenesis to its characteristic bi-lobed shape between the 2- and 3-fold stages of embryogenesis. During this period, the pharyngeal muscles and marginal cells forming the isthmus between the anterior and posterior pharyngeal bulbs elongate and narrow. We have identified the spontaneous mutant pyr-1(cu8) exhibiting defective pharyngeal isthmus elongation, cytoskeletal organization defects, and maternal effect lethality. pyr-1 encodes CAD, a trifunctional enzyme required for de novo pyrimidine synthesis, and pyr-1(cu8) mutants are rescued by supplying exogenous pyrimidines. Similar pharyngeal defects and maternal effect lethality were found in sqv-1, sqv-8, rib-1 and rib-2 mutants, which affect enzymes involved in heparan sulfate proteoglycan (HSPG) synthesis. rib-1 mutant lethality was enhanced in a pyr-1 mutant background, indicating that HSPG synthesis is very sensitive to decreased pyrimidine pools, and HS disaccharides are moderately decreased in both rib-1 and pyr-1 mutants. We hypothesize that HSPGs are necessary for pharyngeal isthmus elongation, and pyr-1 functions upstream of proteoglycan synthesizing enzymes by providing precursors of UDP-sugars essential for HSPG synthesis.     

Frequent Seizures Are Associated with a Network of Gray Matter Atrophy in Temporal Lobe Epilepsy with or without Hippocampal Sclerosis

Objective

Patients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS).

Methods

We evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures.

Results

Patients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions.

Conclusion

Although a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more probably related to the original epileptogenic process.     

tra-2 encodes a membrane protein and may mediate cell communication in the Caenorhabditis elegans sex determination pathway.

The Caenorhabditis elegans sex-determining gene, tra-2, promotes female development in XX animals. In this paper we report the cDNA sequence corresponding to a 4.7 kb tra-2 mRNA and show that it is composed of 23 exons, is trans-spliced to SL2, and contains a perfect direct repeat in the 3' untranslated region. This mRNA is predicted to encode a 1475 amino acid protein, named pTra2A, that has a secretory signal and several potential membrane-spanning domains. The molecular analysis of tra-2 loss-of-function mutations supports our open reading frame identification and suggests that the carboxy-terminal domain is important for tra-2 activity. We propose that in XX animals the carboxy-terminal domain of pTra2A negatively regulates the downstream male promoting fem genes. In XO animals, tra-2 is negatively regulated by her-1, which acts cell nonautonomously. Because hydropathy predictions suggest that pTra2A is an integral membrane protein, pTra2A might act as a receptor for the her-1 protein. We propose that in XO animals, the her-1 protein promotes male development by binding and inactivating pTra2A. The role of cell communication in C. elegans sex determination might be to ensure unified sexual development throughout the animal. If so, then regulation of sexual fate by her-1 and tra-2 might provide a general model for the coordination of groups of cells to follow a single cell fate.     

Sequence Requirements for Myosin Gene Expression and Regulation in Caenorhabditis Elegans

Four Caenorhabditis elegans genes encode muscle-type specific myosin heavy chain isoforms: myo-1 and myo-2 are expressed in the pharyngeal muscles; unc-54 and myo-3 are expressed in body wall muscles. We have used transformation-rescue and lacZ fusion assays to determine sequence requirements for regulated myosin gene expression during development. Multiple tissue-specific activation elements are present for all four genes. For each of the four genes, sequences upstream of the coding region are tissue-specific promoters, as shown by their ability to drive expression of a reporter gene (lacZ) in the appropriate muscle type. Each gene contains at least one additional tissue-specific regulatory element, as defined by the ability to enhance expression of a heterologous promoter in the appropriate muscle type. In rescue experiments with unc-54, two further requirements apparently independent of tissue specificity were found: sequences within the 3' non-coding region are essential for activity while an intron near the 5' end augments expression levels. The general intron stimulation is apparently independent of intron sequence, indicating a mechanistic effect of splicing. To further characterize the myosin gene promoters and to examine the types of enhancer sequences in the genome, we have initiated a screen of C. elegans genomic DNA for fragments capable of enhancing the myo-2 promoter. The properties of enhancers recovered from this screen suggest that the promoter is limited to muscle cells in its ability to respond to enhancers.     

DNA binding and in vivo function of C.elegans PEB-1 require a conserved FLYWCH motif

Caenorhabditis elegans PEB-1 is a novel protein containing a DNA-binding domain in its N terminus, which includes a Cys/His-rich FLYWCH motif also found in Drosophila Mod(mdg4) proteins, and a large C-terminal domain of unknown function. PEB-1 is expressed in most pharyngeal cell types, but its molecular function remains unclear. Here we describe comparative and functional analyses of PEB-1. Characterization of the PEB-1 sequence from C.briggsae indicates highest conservation in the DNA-binding domain (including the FLYWCH motif) and the C terminus, suggesting two functional domains. The PEB-1 FLYWCH motif is essential for DNA-binding and in vivo function; however, it does not bind detectable metal. Likewise, the PEB-1 C terminus is necessary for full activity in vivo, although the DNA-binding domain alone is sufficient for partial function. Both the FLYWCH motif and the C-terminal domain are required for efficient nuclear localization, suggesting PEB-1 must bind DNA and other components to remain in the nucleus. Analysis of binding sites revealed a YDTGCCRW PEB-1 consensus-binding site, and matches to this consensus are widespread in the C.elegans genome.