Metastatic melanoma to the facial nerve

Isolated metastatic malignant melanoma to the facial nerve has never been reported. This presentation illustrates a primary melanoma of the helix of the ear that was treated by excisional biopsy and then wedge resection in 1983. The primary melanoma was Clark's level IV and 1.3 mm in thickness. In 1985, a facial paresis slowly developed. There was no gross evidence of recurrent melanoma in the ear or neck, but CT scan showed a mass in the region of the stylo mastoid foramen. A reoperation of the primary site revealed metastatic melanoma in the facial nerve, expanding it to approximately 10 times its normal size. A composite resection was done for the melanoma, and the paralyzed face was immediately rehabilitated by a masseter muscle transfer. The patient received 6000 rads to this area postoperatively and has remained free of disease to date, having returned to his profession as a dentist. A detailed study of all the specimens indicated that this represented a primary metastasis to the facial nerve.     

Functional Analyses of Endometriosis-Related Polymorphisms in the Estrogen Synthesis and Metabolism-Related Genes

Endometriosis is determined by genetic factors, and the prevalence of genetic polymorphisms varies greatly depending on the ethnic group studied. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of 9 genes involved in estrogen biosynthesis and metabolism and the risks of endometriosis. Three hundred patients with endometriosis and 337 non-endometriotic controls were recruited. Thirty four non-synonymous SNPs, which change amino acid residues, were analyzed using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). The functions of SNP-resulted amino acid changes were analyzed using multiple web-accessible databases and phosphorylation predicting algorithms. Among the 34 NCBI-listed SNPs, 22 did not exhibit polymorphism in this study of more than 600 Taiwanese Chinese women. However, homozygous and heterozygous mutants of 4 SNPs - rs6165 (genotype GG+GA, 307^Ala/Ala+307^Ala/Thr) of FSHR, rs 6166 (genotype GG+GA, 680^Ser/Asn+680^Ser/Ser) of FSHR, rs2066479 (genotype AA+AG, 289^Ser/Ser+289^Ser/Gly) of HSD17B3 and rs700519 (genotype TT+TC, 264^Cys/Cys+264^Cys/Arg) of CYP19, alone or in combination, were significantly associated with decreased risks of endometriosis. Bioinformatics results identified 307^Thr of FSHR to be a site for O-linked glycosylation, 680^Ser of FSHR a phosphorylated site by protein kinase B, and 289^Ser of HSD17B3 a phosphorylated site by protein kinase B or ribosomal protein S6 kinase 1. Results of this study suggest that non-synonymous polymorphisms of FSHR, HSD17B3 and CYP19 genes may modulate the risk of endometriosis in Taiwanese Chinese women. Identification of the endometrosis-preferential non-synonymous SNPs and the conformational changes in those proteins may pave the way for the development of more disease-specific drugs.     

NepA is a structural cell wall protein involved in maintenance of spore dormancy in Streptomyces coelicolor

Streptomycetes have a complex morphogenetic programme culminating in the formation of aerial hyphae that develop into chains of spores. After spore dispersal, environmental signals trigger dormant spores to germinate to establish a new colony. We here compared whole genome expression of a wild-type colony of Streptomyces coelicolor forming aerial hyphae and spores with that of the chp null mutant that forms few aerial structures. This revealed that expression of 244 genes was significantly altered, among which genes known to be involved in development. One of the genes that was no longer expressed in the Δ chpABCDEFGH mutant was nepA , which was previously shown to be expressed in a compartment connecting the substrate mycelium with the sporulating parts of the aerial mycelium. We here show that expression is also detected in developing spore chains, where NepA is secreted to end up as a highly insoluble protein in the cell wall. Germination of spores of a nepA deletion mutant was faster and more synchronous, resulting in colonies with an accelerated morphogenetic programme. Crucially, spores of the Δ nepA mutant also germinated in water, unlike those of the wild-type strain. Taken together, NepA is the first bacterial structural cell wall protein that is important for maintenance of spore dormancy under unfavourable environmental conditions.     

Effects of a chromogranin-derived peptide (CgA 47-66) in the writhing nociceptive response induced by acetic acid in rats

Chromogranin A (CgA) is an acidic protein identified within a large variety of endocrine cells. Colocalized with catecholamines in chromaffin cells, CgA is a prohormone precursor of small biologically active peptides. Vasostatin (CgA 1-76) is the most conserved fragment of CgA and chromogranin A 47-66 peptide (CgA 47-66) possesses potent antimicrobial activities. The aim of this study was to test the hypothesis that CgA 47-66 may be involved in mechanisms modulating nociception. Thus, we used acetic acid (AA) which produces a delayed inflammatory response and episodes of abdominal writhing, a marker of pain, when injected intraperitoneally (i.p.) to rats. Administration (i.p.) of CgA 47-66 induced specific opposite dose-dependent effects depending on concentration. That is, CgA 47-66 below 0.5 mg/kg produced antinociceptive effects, whereas at 2 mg/kg it produced a marked pronociceptive effect. The latter effect was blocked by diltiazem and indomethacin. CgA 47-66-induced antinociceptive effects on AA-induced responses were reversed when the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF 9-41 was i.p. injected to animals prior to AA and CgA 47-66 administration. The administration of i.p. calcitonin gene-related peptide (CGRP) or substance P (SP) evoked dose-dependent abdominal writhing; this effect was abolished when CgA 47-66 was injected. The present data suggest, for the first time, that a fragment of CgA, CgA 47-66, possesses potent antinociceptive effects at low doses. Although the mechanism triggered by this peptide is unknown, CRF receptors are likely to be involved.     

Mal3, the fission yeast EB1 homologue, cooperates with Bub1 spindle checkpoint to prevent monopolar attachment

Bipolar microtubule attachment is central to genome stability. Here, we investigate the mitotic role of the fission yeast EB1 homologue Mal3. Mal3 shows dynamic inward movement along the spindle, initial emergence at the spindle pole body (SPB) and translocation towards the equatorial plane, followed by sudden disappearance. Deletion of Mal3 results in early mitotic delay, which is dependent on the Bub1, but not the Mad2, spindle checkpoint. Consistently, Bub1, but not Mad2, shows prolonged kinetochore localization. Double mutants between mal3 and a subset of checkpoint mutants, including bub1, bub3, mad3 and mph1, but not mad1 or mad2, show massive chromosome mis-segregation defects. In mal3bub1 mutants, both sister centromeres tend to remain in close proximity to one of the separating SPBs. Further analysis indicates that mis-segregated centromeres are exclusively associated with the mother SPB. Mal3, therefore, has a role in preventing monopolar attachment in cooperation with the Bub1/Bub3/Mad3/Mph1-dependent checkpoint.     

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

BackgroundFirst-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer).ConclusionsIndividuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population.     

Effects of phosphinotricin treatment on glutamine synthetase isoforms in Scots pine seedlings

The occurrence of GS isoenzymes has been investigated in Scots pine (Pinus sylvestris) seedlings. A transient increase of glutamine synthetase (GS, EC 6.3.1.2) activity was observed in the cotyledon whorl of plants treated with the herbicide phosphinotricin (PPT). The increase in GS activity was accompanied by a parallel accumulation of GS1 protein, which remained at high levels throughout the PPT treatment. Two-dimensional SDS-PAGE western analysis showed that pine extracts contained two GS1 polypeptides which differ in their corresponding isoelectric points. Analysis of crude extracts by ion-exchange chromatography led to the separation of two GS isoforms. The first peak (GS1-a) eluted from the columns at a low ionic strength (0.15-0.18 M KCl), whereas the second one (GS1-b) was detected at 0.5 M KCl. A detailed molecular study of both GS holoenzymes confirmed that their subunits were similar in size (about 41 kDa) but different in charge. All these data clearly demonstrate the presence of two GS1 forms in Scots pine cotyledons. Moreover, a comparison of isolated GS isoproteins with the recombinantly expressed Scots pine cytosolic subunit suggests that GS1-a corresponds to the previously characterized cDNA (pGSP114) whereas GS1-b is a minor GS isoenzyme with increased relative abundance in phosphinotricin treated plants.     

Social experiments in the mesoscale: humans playing a spatial prisoner's dilemma

Background

The evolutionary origin of cooperation among unrelated individuals remains a key unsolved issue across several disciplines. Prominent among the several mechanisms proposed to explain how cooperation can emerge is the existence of a population structure that determines the interactions among individuals. Many models have explored analytically and by simulation the effects of such a structure, particularly in the framework of the Prisoner''s Dilemma, but the results of these models largely depend on details such as the type of spatial structure or the evolutionary dynamics. Therefore, experimental work suitably designed to address this question is needed to probe these issues.

Methods and Findings

We have designed an experiment to test the emergence of cooperation when humans play Prisoner''s Dilemma on a network whose size is comparable to that of simulations. We find that the cooperation level declines to an asymptotic state with low but nonzero cooperation. Regarding players'' behavior, we observe that the population is heterogeneous, consisting of a high percentage of defectors, a smaller one of cooperators, and a large group that shares features of the conditional cooperators of public goods games. We propose an agent-based model based on the coexistence of these different strategies that is in good agreement with all the experimental observations.

Conclusions

In our large experimental setup, cooperation was not promoted by the existence of a lattice beyond a residual level (around 20%) typical of public goods experiments. Our findings also indicate that both heterogeneity and a “moody” conditional cooperation strategy, in which the probability of cooperating also depends on the player''s previous action, are required to understand the outcome of the experiment. These results could impact the way game theory on graphs is used to model human interactions in structured groups.