Skipping of exon 30 in C5 gene results in complete human C5 deficiency and demonstrates the importance of C5d and CUB domains for stability

The deficiency of complement C5 is rare and frequently associated with severe and recurrent infections, especially caused by Neisseria spp. We observed the absence of component C5 in the serum of 3 siblings from a Brazilian family with history of consanguinity. The patients had suffered from recurrent episodes of meningitis and other less severe infections. Sera from these patients were unable to mediate hemolytic activity either by the classical or alternative pathways and presented extremely low levels of C5 protein (13, 0.9 and 1.0 mu g/ml-normal range: 45-190 mu g/ml). Hemolytic activity could be restored by the addition of purified C5 to deficient serum. Sequencing of sibling C5 cDNA revealed a homozygous 153 bp deletion that corresponds precisely to exon 30. The parents carried the same deletion but only in one allele. Sequencing of the corresponding region in the genomic DNA revealed a C to C substitution within intron 30 and, most significantly, the substitution of GAG(4028) for GAA(4028) at the 3` end of exon 30 which is most likely responsible for skipping of exon 30. The resulting in-frame deletion in the C5 mRNA codes for a mutant C5 protein lacking residues 1289-1339. These residues map to the CUB and C5d domains of the C5 alpha chain. This deletion is expected to produce a non-functional and unstable C5 protein which is more susceptible to degradation. (C) 2009 Published by Elsevier Ltd.

C5 and C6 human dermatomes: a clinical, electromyographical, imaging and surgical findings

There is substantial controversy in literature about human dermatomes. In this work, C5 and C6 superior limb dermatomes were studied. The method consisted of comparing clinical signs and symptoms with conduction studies, electromyographical data, neurosurgical findings, and imaging findings obtained by computerized tomography (CT) or magnetic resonance imaging (MRI), for each patient. Data analysis from superior members in 18 patients suggests that C5 is located in the lateral aspect of the shoulder and arm, and C6 in the lateral aspect of the forearm and 1(st), 2(nd), and 3(rd) fingers. To our knowledge this is the first time that C5 and C6 human dermatomes have been studied by all the following methods together: clinical, electromyographical, CT and MR imaging, and surgical findings.

Comparison between the C5 or C6-Cz electrode assembly and C3 or C4-Cz assembly for transcranial electric motor activation of muscular response of the contralateral facial nerve

We used an assembly of electrodes C3 and C4-Cz in order to activate the motor cortical area of the corticobulbar tract to elucidate the motor-evoked potential of the contralateral mentalis muscle. We compared this setup to that of an assembly with electrodes C5 or C6-Cz using a train of electrical pulses and a single electrical pulse. This analysis was made in 23 consecutive patients who underwent several varied surgeries and were prospectively operated on at Santa Paula Hospital between January and June 2011. The results showed that the assembly with C5 or C6-Cz produced a multisynaptic motor-evoked potential in the contralateral mentalis muscle in 86.9 % of the patients, whereas 82.6 % of patients stimulated at points C3 or C4-Cz presented the same response. However, both assemblies showed similar behavior with the use of a single electrical pulse for peripheral contralateral nerve stimulation. We concluded that the C5 or C6-Cz assembly was similar to C3 or C4-Cz in obtaining a multisynaptic response in the contralateral mentalis muscle, although it required less intensive stimulation than the C3 or C4- Cz assembly.

Combined inhibition of complement C5 and CD14 markedly attenuates inflammation, thrombogenicity, and hemodynamic changes in porcine sepsis

Complement and the TLR family constitute two important branches of innate immunity. We previously showed attenuating effects on inflammation and thromogenicity by inhibiting the TLR coreceptor CD14 in porcine sepsis. In the present study, we explored the effect of the C5 and leukotriene B4 inhibitor Ornithodoros moubata complement inhibitor (OmCI; also known as coversin) alone and combined with anti-CD14 on the early inflammatory, hemostatic, and hemodynamic responses in porcine Escherichia coli-induced sepsis. Pigs were randomly allocated to negative controls (n = 6), positive controls (n = 8), intervention with OmCI (n = 8), or with OmCI and anti-CD14 (n = 8). OmCI ablated C5 activation and formation of the terminal complement complex and significantly decreased leukotriene B4 levels in septic pigs. Granulocyte tissue factor expression, formation of thrombin-antithrombin complexes (p < 0.001), and formation of TNF-α and IL-6 (p < 0.05) were efficiently inhibited by OmCI alone and abolished or strongly attenuated by the combination of OmCI and anti-CD14 (p < 0.001 for all). Additionally, the combined therapy attenuated the formation of plasminogen activator inhibitor-1 (p < 0.05), IL-1β, and IL-8, increased the formation of IL-10, and abolished the expression of wCD11R3 (CD11b) and the fall in neutrophil cell count (p < 0.001 for all). Finally, OmCI combined with anti-CD14 delayed increases in heart rate by 60 min (p < 0.05) and mean pulmonary artery pressure by 30 min (p < 0.01). Ex vivo studies confirmed the additional effect of combining anti-CD14 with OmCI. In conclusion, upstream inhibition of the key innate immunity molecules, C5 and CD14, is a potential broad-acting treatment regimen in sepsis as it efficiently attenuated inflammation and thrombogenicity and delayed hemodynamic changes.

Organ inflammation in porcine Escherichia coli sepsis is markedly attenuated by combined inhibition of C5 and CD14.

Sepsis is an infection-induced systemic inflammatory syndrome, potentially causing organ failure. We previously showed attenuating effects on inflammation, thrombogenicity and haemodynamics by inhibiting the Toll-like receptor co-factor CD14 and complement factor C5 in a porcine Escherichia coli-induced sepsis model. The present study explored the effect on organ inflammation in these pigs. Tissue samples were examined from the combined treatment group (n = 8), the positive (n = 8) and negative (n = 6) control groups after 4h of sepsis. Inflammatory biomarkers were measured using ELISA, multiplex and qPCR analysis. Combined inhibition of C5 and CD14 markedly attenuated IL-1β by 31-66% (P < 0.05) and IL-6 by 54-96% (P < 0.01) in liver, kidney, lung and spleen; IL-8 by 65-100% in kidney, lung, spleen, and heart (P < 0.05) and MCP-1 by 46-69% in liver, kidney, spleen and heart (P < 0.05). Combined inhibition significantly attenuated tissue factor mRNA upregulation in spleen (P < 0.05) and IP-10 mRNA upregulation in four out of five organs. Finally, C5aR mRNA downregulation was prevented in heart and kidney (P < 0.05). Combined inhibition of C5 and CD14 thus markedly attenuated inflammatory responses in all organs examined. The anti-inflammatory effects observed in lung and heart may explain the delayed haemodynamic disturbances observed in septic pigs receiving combined inhibition of C5 and CD14.

C1-C5 hydrocarbons from core gas pockets at DSDP Leg 56 Holes

C1-C5 hydrocarbons from DSDP Legs 56 and 57 sediment gas pockets were analyzed on board ship. Results suggest that the C2-C5 hydrocarbons accompanied biogenic methane and were generated at low temperatures - less than 50° C - either by microorganisms or by low-temperature chemical reactions. Neopentane, a rare constituent of petroleum, is the major C5 component (about 80%) in much of the sediment at Site 438. This compound, which appeared in smaller amounts at Sites 434, 439, 440, and 441, seems to correlate with either fractured or coarse-grained sediments. Scatter in C4 and C5 isomer ratios and generally good correlation between C3, C4 and C5 components suggest local sources for these molecules.

Various ratios of C1-C5 hydrocarbons, gas composition and computed temperature at DSDP Leg 64 Holes

I have evaluated shipboard data and preliminary interpretations related to organic geochemistry in light of additional shore-based analyses. Data on interstitial gas, the C/N ratio, and fluorescence indicate that organic matter was altered by sills and that these were all single intrusions except the upper sill complex at Site 481, which was a multiple emplacement. Site 477 had the highest in situ temperature, estimated from interstitial gas composition to be 225°C.

Time series of zooplankton abundance at station L4 in the English Channel from 1988 to 2011

Ongoing zooplankton research at the Plymouth Marine Laboratory has established a time series of zooplankton species since 1988 at L4, a coastal station off Plymouth. Samples were collected by vertical net hauls (WP2 net, mesh 200 µm; UNESCO 1968) from the sea floor (approximately 50 m) to the surface and stored in 4% formalin. Much of the zooplankton analysis has been to the level of "major taxonomic groups" only, and a number of different analysts have participated over the years. The level of expertise has generally been consistent, but the user should be aware that levels of taxonomic discrimination may vary during the course of the dataset. The dominant calanoid copepods are generally well discriminated to species throughout. Calanus has not been routinely examined for species determination, the assumption being that the local population is entirely composed of Calanus helgolandicus. In certain years there has been a particular interest in Temora stylifera, Centropages cherchiae and other species reflected in the dataset. The lack of records in other previous years does not necessarily reflect species absence. We view it as essential for all users of L4 plankton data to establish and maintain contact with the nominated current data originators as well as fully consulting the metadata. While not impinging on free data access, this ensures that this large, species-rich but slightly complex species database is being used in the correct way, and any potential issues with the data are clarified. Furthermore, a proper dialogue with these local experts on the time series will enable where appropriate the most recent sampling timepoints to be used. The data can be downloaded from BODC or from doi:10.1594/PANGAEA.778092 as files for each year by searching for "L4 zooplankton". The most comprehensive dataset is the version downloadable directly from this page. The entire set of zooplankton samples is stored at the Plymouth Marine Laboratory in buffered formalin, and may be available for further taxonomic analysis on request.