Socio-economic status and mortality in people with type 1 diabetes in Scotland 2006-2015: a retrospective cohort study.

AIMS: To describe the association between socio-economic status and mortality in a nation-wide cohort of people with type 1 diabetes in Scotland and to compare patterns over time and with the general population. METHODS: A retrospective cohort study was performed using data for people with type 1 diabetes from a population-based register linked to mortality records. Socio-economic status was derived from quintiles of an area-based measure: the Scottish Index of Multiple Deprivation. Sex-specific directly age-standardized mortality rates for each Scottish Index of Multiple Deprivation quintile and rate ratios comparing the most vs least deprived quintile were calculated for two time periods: 2006-2010 and 2011-2015. Data for the population without type 1 diabetes between 2011 and 2015 were available for comparison. RESULTS: Data for 3802 deaths among 33 547 people with type 1 diabetes were available. The age-standardized mortality rate per 1000 person-years decreased over time (from 2006-2010 to 2011-2015) for men and women with type 1 diabetes: 24.8 to 20.2 and 22.5 to 17.6, respectively. Mortality in populations with and without type 1 diabetes was generally higher for men than women and was inversely associated with socio-economic status. Rate ratios for the most vs least deprived groups increased over time among people with type 1 diabetes (men: 2.49 to 2.81; women: 1.92 to 2.86) and were higher than among populations without type 1 diabetes in 2011-2015 (men: 2.06; women: 1.66). CONCLUSIONS: Socio-economic deprivation was associated with a steeper mortality gradient in people with type 1 diabetes than in the population without type 1 diabetes in Scotland. Age-standardized mortality has decreased over time but socio-economic inequalities may be increasing.

Network Formation of DNA/Polyelectrolyte Fibrous Aggregates Adsorbed at the Water-Air Interface.

It is discovered that complexes of DNA and hydrophobically modified polyelectrolytes form a rigid network of threadlike or fibrous aggregates at the liquid-gas interface whose morphology can dramatically affect the mechanical properties. While mixed solutions of DNA and poly(N,N-diallyl-N,N-dimethylammonium chloride) (PDADMAC) exhibit no notable surface activity, the complexes formed from DNA with poly(N,N-diallyl-N-butyl-N-methylammonium chloride) are surface-active, in contrast to either of the separate components. Further, complexes of DNA and poly(N,N-diallyl-N-hexyl-N-methylammonium chloride) (PDAHMAC) with its longer hydrophobic side chains exhibit pronounced surface activity with values of surface pressures up to 16 mN/m and dynamic surface elasticity up to 58 mN/m. If the PDAHMAC nitrogen to DNA phosphate molar ratio, N/P, is between 0.6 and 3, abrupt compression of the adsorption layer leads unexpectedly to a noticeable decrease of the surface elasticity. The application of imaging techniques reveals that this effect is a consequence of the destruction of a rigid network of threadlike DNA/polyelectrolyte aggregates at the interface. The toroidal aggregates, which are typical for the bulk phase of DNA/PDADMAC solutions in this range of N/P ratios, are not observed in the surface layer. The observed link between the mechanical properties and interfacial morphology of surface-active complexes formed from DNA with hydrophobically modified polyelectrolytes indicates that tuning polyelectrolyte hydrophobicity in these systems may be a means to develop their use in applications ranging from nonviral gene-delivery vehicles to conductive nanowires.

Effect of Liver Disease Etiology on ROTEM Profiles in Patients Undergoing Liver Transplantation.

BACKGROUND: Coagulation abnormalities in liver transplant patients are complex and may be related to the underlying liver disease. We evaluated the effects of disease etiology on whole-blood rotational thromboelastometry (ROTEM; Pentapharm GmbH, Munich, Germany) profile and association with thrombotic complications following liver transplantation. METHODS: Analysis of perioperative data from patients undergoing liver transplantation between January 1, 2012 and December 31, 2016. Patients were grouped based on the biology of their underlying liver disease: hepatocellular carcinoma (HCC), biliary etiology, and non-biliary etiology. The primary outcome was the EXTEM A10 value of the pre-incision ROTEM. Secondary outcomes included associations between EXTEM A10 value and incidence of postoperative thrombotic complications. RESULTS: Three hundred fifty patients met the eligibility criteria: 60 had biliary etiologies, 203 had non-biliary etiologies, and 87 had HCC. EXTEM A10 values were significantly higher in patients with biliary etiologies than those with non-biliary etiologies (mean difference, 13.8; 95% CI: 10.1 to 17.5; P = .001) and those with HCC (mean difference, 10.4; 95% CI: 6.2 to 14.7; P = .001). Patients with non-biliary etiologies had slightly higher values than those with HCC (mean difference, -3.3; 95% CI: -6.6 to -0.1; P = .04). Higher values for biliary etiologies remained after adjusting for liver disease severity, platelet count, and fibrinogen level. There was no significant difference in EXTEM A10 values between patients who suffered thrombotic complications and those who did not (mean difference: 4.3, 95% CI: -1.3 to 9.9, P = .13). CONCLUSION: Patients with biliary diseases demonstrated higher EXTEM A10 values compared to those with non-biliary diseases or HCC. This was not fully explained by differences in disease severity, platelet count, or fibrinogen level. Pre-incision EXTEM A10 values do not predict incidence of postoperative thrombotic complications.

Neutron reflectivity measurements at the oil/water interface for the study of stimuli-responsive emulsions⋆.

Stable stimuli-responsive emulsions between oil and water are formed with an amphiphilic block copolymer bearing polystyrene (PS) and poly(dimethylaminoethyl methacrylate) (PDMAEMA) moieties. Different kinds of emulsions like direct, multiple or inverse ones are reproducibly formed as a function of chemical parameters such as p H and salt concentration. To test the correlation between the different nature of the emulsion and the conformation of the polymer chain at the interface, neutron reflectometry at the oil/water interface was carried out. An original sample cell was built and the procedure to get reliable results with it on the FIGARO reflectometer at the Institut Laue-Langevin is described. Results show that for direct emulsions, the copolymer is much more extended on the water side than on the oil side. In the case where multiple emulsions are stabilized, the conformation is strongly modified and is compatible with a more equilibrated extension of the chain on both sides. The inverse case shows that the extension in oil is stronger than in water. These results are discussed in term of polymer brushes (charged or neutral) extension with respect to salt addition and hydrophobic interactions.

PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway.

Essentials Phosphoinositide 3-kinase and MAPK pathways crosstalk via PDK1. PDK1 is required for adenosine diphosphate-induced platelet activation and thromboxane generation. PDK1 regulates RAF proto-oncogene Ser/Thr kinase (Raf1) activation in the MAPK pathway. Genetic ablation of PDK1 protects against platelet-dependent thrombosis in vivo. SUMMARY: Background Platelets are dynamic effector cells with functions that span hemostatic, thrombotic and inflammatory continua. Phosphoinositide-dependent protein kinase 1 (PDK1) regulates protease-activated receptor 4-induced platelet activation and thrombus formation through glycogen synthase kinase3ß. However, whether PDK1 also signals through the ADP receptor and its functional importance in vivo remain unknown. Objective To establish the mechanism of PDK1 in ADP-induced platelet activation and thrombosis. Methods We assessed the role of PDK1 on 2MeSADP-induced platelet activation by measuring aggregation, thromboxane generation and phosphorylation events in the presence of BX-795, which inhibits PDK1, or by using platelet-specific PDK1 knockout mice and performing western blot analysis. PDK1 function in thrombus formation was assessed with an in vivo pulmonary embolism model. Results PDK1 inhibition with BX-795 reduced 2-methylthio-ADP (2MeSADP)-induced aggregation of human and murine platelets by abolishing thromboxane generation. Similar results were observed in pdk1-/- mice. PDK1 was also necessary for the phosphorylation of mitogen-activated protein kinase kinase 1/2 (MEK1/2), extracellular signal-regulated kinase 1/2, and cytosolic phospholipase A2, indicating that PDK1 regulates an upstream kinase in the mitogen-activated protein kinase (MAPK) pathway. We next determined that this upstream kinase is Raf-1, a serine/threonine kinase that is necessary for the phosphorylation of MEK1/2, as pharmacological inhibition and genetic ablation of PDK1 were sufficient to prevent Raf1 phosphorylation. Furthermore, in vivo inhibition or genetic ablation of PDK1 protected mice from collagen/epinephrine-induced pulmonary embolism. Conclusion PDK1 governs thromboxane generation and thrombosis in platelets that are stimulated with 2MeSADP by regulating activation of the MAPK pathway.

Determination of cyclic volatile methylsiloxanes in personal care products by gas chromatography.

OBJECTIVE: Organosiloxanes are prevalent in personal care products (PCPs) due to the desired properties they impart in the usage and application of such products. However, the European Chemical Agency (ECHA) has recently published restriction proposals on the amount of two cyclic siloxanes, octamethylcyclotetrasiloxane (D4) and decamethylcyclotetrasiloxane (D5), allowed in wash off products such as shampoos and conditioners which are discharged down the drain during consumer use. This legislation will require that reliable analytical methods are available for manufacturers and government agencies to use in documenting compliance with the restrictions. This article proposes a simple analytical method to enable accurate measurement of these compounds down to the circa 0.1 weight per cent level in PCPs. METHODS: Although gas chromatography methods are reported in the literature for quantitation of D4 and D5 in several matrices including PCPs, the potential for generation of false positives due to contamination, co-elution and in situ generation of cyclic volatile methylsiloxanes (cVMS) is always present and needs to be controlled. This report demonstrates the applicability of using a combination of emulsion break, liquid-liquid extraction and silylation sample preparation followed by GC-FID analysis as a suitable means of analysing PCPs for specific cVMS. RESULTS: The reliability and limitations of such methodology were demonstrated through several round-robin studies conducted in the laboratories of a consortium of silicone manufacturers. In addition, this report presents examples of false positives encountered during development of the method and presents a comparative analysis between this method and a published QuEChERS sample preparation procedure to illustrate the potential for generation of false positives when an inappropriate approach is applied to determination of cVMS in personal care products. CONCLUSION: This report demonstrates that an approach to determine cVMS levels in personal care products is to perform an emulsion break on the sample, isolate the non-polar phase from the emulsion break and treat with a silylation reagent to abate potential in situ formation of cyclics during the course of GC-FID analysis. Round-robin studies conducted in laboratories representing multiple siloxane manufacturers demonstrated the reliability of the GC-FID method when measuring cVMS in PCPs down to circa 0.1%.

Resting-state brain alteration after a single dose of SSRI administration predicts 8-week remission of patients with major depressive disorder.

BACKGROUND: The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment. METHOD: Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement. RESULTS: Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint. CONCLUSIONS: This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.

Combined variants in factor VIII and prostaglandin synthase-1 amplify hemorrhage severity across three generations of descendants.

Essentials Co-existent damaging variants are likely to cause more severe bleeding and may go undiagnosed. We determined pathogenic variants in a three-generational pedigree with excessive bleeding. Bleeding occurred with concurrent variants in prostaglandin synthase-1 (PTGS-1) and factor VIII. The PTGS-1 variant was associated with functional defects in the arachidonic acid pathway. SUMMARY: Background Inherited human variants that concurrently cause disorders of primary hemostasis and coagulation are uncommon. Nevertheless, rare cases of co-existent damaging variants are likely to cause more severe bleeding and may go undiagnosed. Objective We prospectively sought to determine pathogenic variants in a three-generational pedigree with excessive bleeding. Patients/methods Platelet number, size and light transmission aggregometry to multiple agonists were evaluated in pedigree members. Transmission electron microscopy determined platelet morphology and granule content. Thromboxane release studies and light transmission aggregometry in the presence or absence of prostaglandin G2 assessed specific functional defects in the arachidonic acid pathway. Whole exome sequencing (WES) and targeted nucleotide sequence analysis identified potentially deleterious variants. Results Pedigree members with excessive bleeding had impaired platelet aggregation with arachidonic acid, epinephrine and low-dose ADP, as well as reduced platelet thromboxane B2 release. Impaired platelet aggregation in response to 2MesADP was rescued with prostaglandin G2 , a prostaglandin intermediate downstream of prostaglandin synthase-1 (PTGS-1) that aids in the production of thromboxane. WES identified a non-synonymous variant in the signal peptide of PTGS-1 (rs3842787; c.50C>T; p.Pro17Leu) that completely co-segregated with disease phenotype. A variant in the F8 gene causing hemophilia A (rs28935203; c.5096A>T; p.Y1699F) was also identified. Individuals with both variants had more severe bleeding manifestations than characteristic of mild hemophilia A alone. Conclusion We provide the first report of co-existing variants in both F8 and PTGS-1 genes in a three-generation pedigree. The PTGS-1 variant was associated with specific functional defects in the arachidonic acid pathway and more severe hemorrhage.

Structure of a liquid/liquid interface during solvent extraction combining X-ray and neutron reflectivity measurements.

We have resolved the molecular structure of a bulk oil/water interface that contains amphiphilic ligand molecules using a combination of X-ray and neutron reflectivity measurements for the first time. This new capability can greatly impact future work in the field of ion separation by phase transfer, i.e. liquid/liquid extraction.

"Satan has afflicted me!" Jinn-possession and mental illness in the Qur'an.

Mental health stigma in Muslim communities may be partly due to a commonly held belief among some Muslims about the supernatural causes of mental illness (i.e. jinn-possession brought on by one's sinful life). A thematic analysis was carried out on four English translations and the Arabic text of the Qur'an to explore whether the connection between jinn-possession and insanity exists within the Muslim holy book. No connection between spirit-possession and madness or mental illness was found. Pagans taunted and labelled people as jinn-possessed only to ostracize and scapegoat. Linking the labelling of people as jinn-possession to a pagan practice may be used to educate Muslims, so they can reassess their community's stigma towards the mentally ill.

Effect of helper lipids on the interaction of DNA with cationic lipid monolayers studied by specular neutron reflection.

The interaction of DNA with monolayers of the cationic lipid dimethyldioctadecylammonium bromide, with/without 50 mol % of a neutral "helper" lipid, either dioleoylphosphatidylethanolamine or cholesterol, has been studied using specular neutron reflection, surface pressure-area isotherms, and Brewster angle microscopy. The amount of DNA bound to the lipid head groups has been comprehensively quantified in the range of 8-39 vol% of DNA with respect to the monolayer composition (monolayers composed of dimethyldioctadecylammonium bromide binding the most DNA and monolayers containing dioleoylphosphatidylethanolamine binding the least) and surface pressure (DNA binding being greatest at highest surface pressures). Surprisingly, regardless of these variables, the thickness of the DNA-containing layer remained approximately constant between 18 and 25 Å. This systematic study is the first direct quantification of the binding of DNA with two different helper-lipid-containing multicomponent monolayers, an important step toward understanding interaction parameters in more realistic models of gene delivery systems.

Bathygrillotia n. g. (Cestoda: Trypanorhyncha), with redescriptions of B. rowei (Campbell, 1977) n. comb. and B. kovalevae (Palm, 1995) n. comb.

Bathygrillotia n. g. (Cestoda: Trypanorhyncha) is erected for B. rowei (Campbell, 1977) n. comb. and B. kovalevae (Palm, 1995) n. comb. The new genus is based on the possession of two bothria, an atypical, heteroacanthous, heteromorphous armature with longitudinal files of hooks on the external surface of the tentacle associated with each principal row, each consisting of a large anterior hook followed by two smaller hooks. Bathygrillotia is allocated to the Lacistorhynchoidea Guiart, 1927 and its relationships with Grillotia Guiart, 1927 are discussed.

The effect of neutral helper lipids on the structure of cationic lipid monolayers.

Successful drug delivery via lipid-based systems has often been aided by the incorporation of 'helper lipids'. While these neutral lipids enhance the effectiveness of cationic lipid-based delivery formulations, many questions remain about the nature of their beneficial effects. The structure of monolayers of the cationic lipid dimethyldioctadecylammonium bromide (DODAB) alone, and mixed with a neutral helper lipid, either diolelyphosphatidylethanolamine or cholesterol at a 1 : 1 molar ratio was investigated at the air-water interface using a combination of surface pressure-area isotherms, Brewster angle microscopy (BAM) and specular neutron reflectivity in combination with contrast variation. BAM studies showed that while pure DODAB and DODAB with cholesterol monolayers showed fairly homogeneous surfaces, except in the regions of phase transition, monolayers of DODAB with diolelyphosphatidylethanolamine were, in contrast, inhomogeneous exhibiting irregular bean-shaped domains throughout. Neutron reflectivity data showed that while the thickness of the DODAB monolayer increased from 17 to 24 Å as it was compressed from a surface pressure of 5-40 mN m(-1), the thickness of the helper lipid-containing monolayers, over the same range of surface pressures, was relatively invariant at between 25 and 27 Å. In addition, the monolayers containing diolelyphosphatidylethanolamine were found to be more heavily hydrated than the monolayers of cationic lipid, alone or in combination with cholesterol, with hydration levels of 18 molecules of water per molecule of lipid being recorded for the diolelyphosphatidylethanolamine-containing monolayers at a surface pressure of 30 mN m(-1) compared with only six and eight molecules of water per molecule of lipid for the pure DODAB monolayer and the cholesterol-containing DODAB monolayer, respectively.

The septic milieu triggers expression of spliced tissue factor mRNA in human platelets.

BACKGROUND: Activated platelets have previously-unrecognized mechanisms of post-transcriptional gene expression that may influence hemostasis and inflammation. A novel pathway involves splicing of pre-mRNAs in resting platelets to mature, translatable mRNAs in response to cellular activation. OBJECTIVES: We asked if bacterial products and host agonists present in the septic milieu induce tissue factor pre-mRNA splicing in platelets from healthy subjects. In parallel, we asked if spliced tissue factor (TF) mRNA is present in platelets from septic patients in a proof-of-principle analysis. PATIENTS/METHODS: TF pre-mRNA and mRNA expression patterns were characterized in platelets from septic patients and in platelets isolated from healthy subjects activated with bacteria, toxins and inflammatory agonists. Procoagulant activity was also measured. RESULTS AND CONCLUSIONS: Live bacteria, staphylococcal α-toxin and lipopolysaccharide (LPS) induced TF pre-mRNA splicing in platelets isolated from healthy subjects. Toxin-stimulated platelets accelerated plasma clotting, a response that was blocked by a previously-characterized splicing inhibitor and by an anti-tissue factor antibody. Platelets from septic patients expressed spliced TF mRNA, whereas it was absent from unselected and age-matched control subjects. Tissue factor-dependent procoagulant activity was elevated in platelets from a subset of septic patients. Thus, bacterial and host factors induce splicing of TF pre-mRNA, expression of TF mRNA and tissue factor-dependent clotting activity in human platelets. TF mRNA is present in platelets from some septic patients, indicating that it may be a marker of altered platelet phenotype and function in sepsis and that splicing pathways are induced in this syndrome.

Validation of Christianella Guiart, 1931 (Cestoda: Trypanorhyncha) and its taxonomic relationship with Grillotia Guiart, 1927.

Christianella Guiart, 1931 (Cestoda: Trypanorhyncha) is redefined as a subgenus of Grillotia Guiart, 1927 based on the type-species, G. (C.) minuta (van Beneden, 1849), from the elasmobranch Squatina squatina (Linnaeus). Grillotia smarisgora (Wagener, 1854) is treated as a synonym of G. (C.) minuta, as are G. angeli Dollfus, 1969 and G. bothridiopunctata Dollfus, 1969. Other species included in the subgenus are G. (C.) carvajalregorum Menoret & Ivanov, 2009 (formerly Progrillotia dollfusi Carvajal & Rego, 1983), G. (C.) australis Beveridge & Campbell, 2001, G. (C.) longispinis (Linton, 1890) n. comb. (formerly Rhynchobothrium longispine Linton, 1890) and G. (C.) yuniariae Palm, 2004. The subgenus is similar to Grillotia Guiart, 1927 (sensu stricto), having two bothria and an atypical heteroacanthous armature, but differs in having a single row of intercalary hooks, fewer, elongate segments with testes often in longitudinal columns, a distinctive basal armature, an internal seminal vesicle which extends beyond the cirrus or hermaphroditic sac and no uterine pore. The adults of three species are known, all parasitising members of Squatina Duméril.

Enhanced cell-associated plasminogen activator pathway but not coagulation pathway activity contributes to motility in metastatic breast cancer cells.

BACKGROUND: Activation of tumor cell-associated coagulation and plasminogen activator pathways occurs in malignant disease processes, including breast cancer, and may promote metastatic activity. OBJECTIVES/METHODS: To compare the coagulation and plasminogen activator pathways of normal and metastatic cells, we examined two cell lines from the MCF-10 family of breast cells: near-normal immortalized MCF-10A cells, and metastatic MCF-10CA1 cells. RESULTS: MCF-10CA1 cell motility was significantly increased as compared with that of MCF-10A cells. The two cell types supported similar rates of factor Xa generation, plasma thrombin generation, and fibrin formation. MCF-10A cells produced a stable fibrin network, whereas MCF-10CA1 cells lysed the surrounding fibrin network within 24 h of network formation. Importantly, fibrin located proximal to (within 10 microm) the MCF-10CA1 cell surface lysed substantially faster than fibrin located 100 microm from the surface. MCF-10CA1 cells supported significantly increased plasmin generation rates as compared with MCF-10A cells, providing a mechanism for the increased fibrinolytic activity of these cells towards the fibrin network. Metastatic MCF-10CA1 cells had increased expression (mRNA and protein) levels of urokinase plasminogen activator (u-PA) and decreased levels of plasminogen activator inhibitor-1 as compared with MCF-10A cells. Blocking u-PA activity with the active site-directed protease inhibitor amiloride substantially decreased MCF-10CA1 cell motility. Phosphorylated Akt levels were elevated in MCF-10CA1 cells, which partially explains the increased u-PA expression. CONCLUSIONS: These results suggest that the tumor-associated plasminogen activator pathway, not the coagulation pathway, is a key distinguishing feature between metastatic MCF10-CA1 cells and normal MCF-10A cells.

Islands in the sea: extreme female natal site fidelity in the Australian sea lion, Neophoca cinerea.

Pinnipeds (seals, fur seals, sea lions and walrus) form large breeding aggregations with females often remaining faithful to a natal site or area. In these cases, females are philopatric to regional areas on broad geographical scales of hundreds to thousands of kilometers. An investigation of variation in a control region sequence of mtDNA in the Australian sea lion (Neophoca cinerea) has shown a case of extreme female natal site fidelity that has resulted in almost fixed population differentiation across its range (PhiST=0.93). This high level of population subdivision over short geographical distances (approx. 60 km) is unparalleled in any social marine mammal and reflects the unique life-history traits of this rare species. The high level of population subdivision and exclusive female natal site fidelity has important ramifications for conservation management, and poses many interesting questions of both academic and applied interest.

Revision of the Grillotia erinaceus (van Beneden, 1858) species complex (Cestoda: Trypanorhyncha), with the description of G. brayi n. sp.

Members of the trypanorhynch cestode genus Grillotia Guiart, 1927 belonging to the Grillotia erinaceus (van Beneden, 1858) species complex are redescribed. The type-species of the genus, G. erinaceus, is redescribed from Raja spp. in the eastern and western north Atlantic and the Mediterranean. The redescription establishes the presence of: an hermaphroditic sac; internal and external seminal vesicles (but absence of an accessory seminal vesicle); a uterine pore; and the attachment of the retractor muscle in the mid-region of the tentacular bulb. G. pseuderinaceus Dollfus, 1969 and G. recurvispinis Dollfus, 1969 from Raja spp. in the Mediterranean are considered to be synonyms of G. erinaceus, following Palm (2004). G. dollfusi Carvajal, 1971 from R. chilensis Guichenot off Chile is redescribed from the paratypes and features of the terminal genitalia, consistent with those of G. erinaceus, are described for the first time. G. musculara (Hart, 1936) is redescribed from new material collected from the type-host, R. rhina (Jordan & Gilbert), off Nanaimo on the western coast of Canada. The features of the terminal genitalia of G. musculara are similar to those of the G. erinaceus group. The morphological features of G. borealis Keeney & Campbell, 2001 from Bathyraja spp. in the Bering Sea and the Sea of Okhotsk are summarised and illustrations of this species provided. G. brayi n. sp. is described from Amblyraja radiata from the coasts of Iceland and Britain. The new species differs from other members of the complex in lacking modified hooks 1 and 1' at the base of the tentacle (differentiating it from G. erinaceus), a long pars vaginalis (differentiating it from G. dollfusi) and uncinate hooks in the band on the external surface of the tentacle (differentiating it from G. musculara). Brief descriptions are provided of two apparently new species of Grillotia currently represented in collections by single specimens.

Interference with nuclear factor kappa B and c-Jun NH2-terminal kinase signaling by TRAF6C small interfering RNA inhibits myeloma cell proliferation and enhances apoptosis.

The tumor necrosis factor receptor (TNFR)-associated factor (TRAF) family of six adaptor proteins (TRAF1-6) links the TNFR superfamily to the nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1) transcriptional activators. Unlike other TRAFs, TRAF6 is also involved in Toll-like/interleukin (IL)-1 receptor (TIR) signal transduction. Thus, inhibition of TRAF6 function could interrupt both CD40 (TNFR family) and IL-1 growth signals, pathways critical to myeloma proliferation. To block TRAF6-mediated IL-1 signaling, we constructed small interfering RNA (siRNA) against TRAF6. We found that siRNA targeting the TRAF6 C-terminal (siTRAF6C) receptor interaction domain specifically reduced only TRAF6 protein expression, without affecting TRAF2 or 5 levels, and substantially interfered with IL-1-induced NF-kappaB and c-Jun/AP-1 activation. Inhibition by siTRAF6C was concentration-dependent. SiTRAF6C also significantly reduced myeloma proliferation and enhanced apoptosis in a similar dose-dependent fashion in vitro. More importantly, marked siTRAF6C growth inhibition was detected in vivo when these cells were implanted into the bone marrow of irradiated normal mice. In contrast, introduction of siRNA derived from the TRAF6 Zn-finger domain or an irrelevant siRNA construct failed to alter cell growth or cell death. These studies suggest that TRAF6 may be a new molecular target to block cell signal transduction important for the survival and proliferation of multiple myeloma cells.

Two new species of Pseudochristianella Campbell & Beveridge, 1990 (Cestoda: Trypanorhyncha) from elasmobranch fishes from the Gulf of California, Mexico.

Pseudochristionella elegantissima sp. nov. (Cestoda: Trypanorhyncha) is described from the spiral valves of the rays Dasyatis brevis (Garman, 1880) and D. longus (Garman, 1880), from the Gulf of California, Mexico. Also described is P. nudisculo sp. nov. from rays Rhinobatos productus Ayres, 1854, D. longus, Myliobatis longirostris Applegate & Fitch, 1964 and Zapteryx exasperat (Jordan & Gilbert, 1880) from the same location. The species are distinguished from one another and from the only existing species within the genus, P. southwelli Campbel & Beveridge, 1990, by differences in the arrangement of bill-hooks on the external surface of the basal swelling of the tentacle and by the number of hooks in each row of the metabasasl armature.