Dyes in History and Archaeology 41: Reflections on the Conference and Its Assembly of Articles

Editorial: no abstract availabl

Gene expression level influences amino acid usage, but not codon usage, in the tsetse fly endosymbiont Wigglesworthia

Author Posting. © Society for General Mircobiology, 2003. This article is posted here by permission of Society for General Mircobiology for personal use, not for redistribution. The definitive version was published in Microbiology 149 (2003): 2585-2596, doi:10.1099/mic.0.26381-0.Wigglesworthia glossinidia brevipalpis, the obligate bacterial endosymbiont of the tsetse fly Glossina brevipalpis, is characterized by extreme genome reduction and AT nucleotide composition bias. Here, multivariate statistical analyses are used to test the hypothesis that mutational bias and genetic drift shape synonymous codon usage and amino acid usage of Wigglesworthia. The results show that synonymous codon usage patterns vary little across the genome and do not distinguish genes of putative high and low expression levels, thus indicating a lack of translational selection. Extreme AT composition bias across the genome also drives relative amino acid usage, but predicted high-expression genes (ribosomal proteins and chaperonins) use GC-rich amino acids more frequently than do low-expression genes. The levels and configuration of amino acid differences between Wigglesworthia and Escherichia coli were compared to test the hypothesis that the relatively GC-rich amino acid profiles of high-expression genes reflect greater amino acid conservation at these loci. This hypothesis is supported by reduced levels of protein divergence at predicted high-expression Wigglesworthia genes and similar configurations of amino acid changes across expression categories. Combined, the results suggest that codon and amino acid usage in the Wigglesworthia genome reflect a strong AT mutational bias and elevated levels of genetic drift, consistent with expected effects of an endosymbiotic lifestyle and repeated population bottlenecks. However, these impacts of mutation and drift are apparently attenuated by selection on amino acid composition at high-expression genes.This work was made possible by support to J. J. W. from the NIH (R01 GM62626-01) and NSF (DEB 0089455), and the Josephine Bay Paul and C. Michael Paul Foundation

Preparation and topology of the Mediator middle module

Mediator is the central coactivor complex required for regulated transcription by RNA polymerase (Pol) II. Mediator consists of 25 subunits arranged in the head, middle, tail and kinase modules. Structural and functional studies of Mediator are limited by the availability of protocols for the preparation of recombinant modules. Here, we describe protocols for obtaining pure endogenous and recombinant complete Mediator middle module from Saccharomyces cerevisiae that consists of seven subunits: Med1, 4, 7, 9, 10, 21 and 31. Native mass spectrometry reveals that all subunits are present in equimolar stoichiometry. Ion-mobility mass spectrometry, limited proteolysis, light scattering and small-angle X-ray scattering all indicate a high degree of intrinsic flexibility and an elongated shape of the middle module. Protein–protein interaction assays combined with previously published data suggest that the Med7 and Med4 subunits serve as a binding platform to form the three heterodimeric subcomplexes, Med7N/21, Med7C/31 and Med4/9. The subunits, Med1 and Med10, which bridge to the Mediator tail module, bind to both Med7 and Med4

Combined portal and hepatic vein embolisation in perihilar cholangiocarcinoma

Background: Major hepatectomy in perihilar cholangiocarcinoma (pCCA) patients with a small future liver remnant (FLR) risks posthepatectomy liver failure (PHLF). This study examines combined portal and hepatic vein embolisation (PVE/HVE) to increase preoperative FLR volume and potentially decrease PHLF rates. Methods: In this retrospective, multicentre, observational study, data was collected from centres affiliated with the DRAGON Trials Collaborative and the EuroLVD registry. The study included pCCA patients who underwent PVE/HVE between July 2016 and January 2023. Results: Following PVE/HVE, 28% of patients (9/32) experienced complications, with 22% (7/32) necessitating biliary interventions for cholangitis. The median degree of hypertrophy after a median of 16 days was 16% with a kinetic growth rate of 6.8% per week. 69% of patients (22/32) ultimately underwent surgical resection. Cholangitis after PVE/HVE was associated with unresectability. After resection, 55% of patients (12/22) experienced complications, of which 23% (5/22) were Clavien-Dindo grade III or higher. The 90-day mortality after resection was 0%. Conclusion: PVE/HVE quickly enhances the kinetic growth rate in pCCA patients. Cholangitis impairs chances on resection significantly. Resection after PVE/HVE is associated with low levels of 90-day mortality. The study highlights the potential of PVE/HVE in improving safety and outcomes in pCCA undergoing resection

Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study

Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin(IL)-6, IL-10 and TNF-α and the risk of TC. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1 =0.69, 95%CI: 0.49-0.98, Ptrend =0.04) but not among men (ORT3vs.T1 =1.36, 95%CI: 0.67-2.76, Ptrend =0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1 =1.59, 95%CI: 1.13-2.25, Ptrend =0.01) but not in men (ORT3vs.T1 =1.78, 95%CI: 0.80-3.98, Ptrend =0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight. What's new? How does being overweight lead to thyroid cancer? These authors investigated, using data from the EPIC cohort. Considering obesity as a state of chronic inflammation, they looked at levels of various proteins associated with inflammation, including C-reactive protein, IL-10, adiponectin, and others, and compared these with TC risk. Women with high adiponectin levels were less likely to develop thyroid cancer, while those with high IL-10 levels had increased TC risk. No significant association was seen in men

The neural effects of palytoxinThe neural effects of palytoxin

Palytoxin, the most potent known marine toxin, has been demonstrated to produce acute neurological disturbances in several animal species and, possibly, even in humans. However, the effects of palytoxin on excitable membranes have not been well characterised or explained. Palytoxin occurs within the same ecosystem in which other seafood toxins such as ciguatoxin, saxitoxin and brevetoxins are found. Also, several reports suggest that, occasionally, palytoxin may contribute to the ciguatera syndrome. As these other toxins are known to affect the sodium ion channel, either by activation or inactivation, evidence that palytoxin may also affect this structure was sought. The studies performed on the ventral coccygeal nerve of the rat tail, subsequent to an intraperitoneal injection of palytoxin, demonstrated a significant slowing of mixed nerve and motor conduction velocities and a reduction in the amplitude of the mixed nerve and motor action potentials. However, palytoxin exerted no effect on the latency of the shortest F-wave response. In the palytoxin-treated group, the absolute and relative refractory periods were prolonged. Palytoxin also appeared to induce a significant prolongation of the supernormal period of nerve excitability. The response of the palytoxin-treated ventral coccygeal nerve to repetitive stimulation demonstrated no consistent abnormality. These studies lend indirect support to the proposition that at least one action of palytoxin is that of an alteration in the excitability of neural tissue by inducing persistent sodium ion channel activation. Lignocaine, administered via the intraperitoneal route, was demonstrated to reverse many of the electrophysiological disturbances and, particularly, the prolonged supernormal period, in palytoxin-treated rats. These results suggest that prior activation of sodium ion channels by palytoxin may be blocked by lignocaine. Ethanol, administered via the intraperitoneal route, was observed to reverse many of the electrophysiological disturbances recorded in the palytoxin-treated rats, however, the supernormal period remained prolonged, yet not particularly enhanced or diminished in magnitude. Ouabain, administered via the intraperitoneal route, also reversed many of the electrophysiological disturbances induced in palytoxin-treated rats. However, in these animals, the palytoxin-induced supernormal period remained prolonged, yet not exaggerated or diminished in magnitude. These results suggest that membrane excitability may occur independently of, or with, the (Na+,K+)A TPase mechanism. The effect of palytoxin on mammalian nerve tissue appeared to be modified at a lower temperature. Mixed nerve and motor conduction, F-wave responses, absolute and relative refractory period and supernormal period studies were performed on palytoxin-treated animals at 25°C. The only significant abnormalities were a prolongation of the relative refractory period and of the supernormal period. This study suggests that, at least, in mammalian nerve tissue, this toxin is less active at a lower ambient temperature. In terms of central studies, in palytoxin-treated rats the brainstem auditory evoked response was not significantly altered although there was significant prolongation of the corticospinal evoked response. This finding suggests that palytoxin is capable of crossing the blood-brain barrier and, then, exerting an effect on central nerve membranes. These results are similar to those induced by ciguatoxin in the ventral coccygeal nerve of the rat. Both toxins produce slowing of the mixed nerve and motor conduction velocities, a reduction in the amplitude of the mixed nerve and motor action potentials and a prolongation of the refractory period and supernormal period. Lignocaine abolishes the supernormal period induced by both toxins. At a temperature of 25°C, both toxins produce reduced electrophysiological effects, in comparison with those produced at 37°C. Ciguatoxin is known to bind to and to activate or open sodium ion channels. These studies suggest that at least one action of palytoxin may be that of a similar activation of sodium ion channels. With reference to these studies and to the fact that both toxins occur within the same ecosystem, palytoxin could potentially contribute, on occasions, to the ciguatera syndrome

Tunnels.

Bibliography: p. [415]-417.Mode of access: Internet