The aim of this study was to describe the frequency, attribution, outcome and predictors of seizures in systemic lupus erythematosus (SLE).
The Systemic Lupus International Collaborating Clinics, or ...SLICC, performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLE Disease Activity Index 2000), cumulative organ damage (SLICC/American College of Rheumatology Damage Index (SDI)) and neuropsychiatric events were recorded at enrolment and annually. Lupus anticoagulant, anticardiolipin, anti-β(2) glycoprotein-I, antiribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrolment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 (36-Item Short Form Health Survey) mental component summary and physical component summary scores. Statistical analyses included Cox and linear regressions.
The cohort was 89.4% female with a mean follow-up of 3.5±2.9 years. Of 1631 patients, 75 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07 to 3.63); p=0.03) and lower education status (1.97 (1.21 to 3.19); p<0.01). Higher damage scores (without neuropsychiatric variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46 to 10.55); SDI=2 or 3:1.57 (0.32 to 7.65); SDI≥4:7.86 (0.89 to 69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78 (76%)) in the absence of antiseizure drugs. There was no significant impact on the mental component summary or physical component summary scores. Antimalarial drugs in the absence of immunosuppressive agents were associated with reduced seizure risk (0.07 (0.01 to 0.66); p=0.03).
Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Antimalarial drugs were associated with a protective effect.
Loose smut Ustilago tritici (Pers) Rostr. of wheat (Triticum aestivum L) causes losses in grain yield roughly proportional to the incidence of the disease. Efforts to control this disease utilizing ...genetic resistance are being made in breeding programmes around the world. DNA markers for genetic resistance would greatly enhance breeding efforts by reducing the substantial time and labour resources necessary to screen for resistant lines using traditional inoculation methods. The objective of this study was to identify DNA markers associated with resistance. Doubled haploid progeny from the four crosses ‘Glenlea’/‘AC Taber’, ‘SC8021V2’/‘AC Karma’, ‘Diamant’/TD12A, and 9340-CP*/‘AC Vista’ were evaluated with individual races of U. tritici and simple sequence repeat markers. Simple interval mapping was performed using MQTL software and single point analysis. ‘Glenlea’, which has complete and broad resistance to all known races of U. tritici in Canada, contributed a QTL for resistance to races T2, T10, T15, T19 and T39 at Xwmc160 on chromosome 5B. ‘Glenlea’ also contributed QTL for resistance to races T2, T9 and T15 at Xgwm302 on chromosome 7B and to races T9, T19 and T39 on chromosome 3A at marker Xwmc559 . The chromosome 5B QTL from ‘Glenlea’ coincided with a race T39 resistance locus from ‘AC Karma’. The 7B QTL from ‘Glenlea’ coincided with resistance to race T9 from 9340-CP* and T2, T9 and T27 resistance from TD12A. The QTL on 3A from ‘Glenlea’ was coincidental with T9 resistance from 9340-CP*. When evaluated with race T10, a QTL was identified near Xbarc183 on chromosome 6D from ‘SC8021V2’. A QTL to race T9 from ‘SC8021V2’ within the interval Xcfa2019 to Xgwm344a was identified on 7A. A third QTL from ‘SC8021V2’ was located on 6B at Xbarc223 and Xbarc332b. The chromosome 5B locus together with either the 7A or 7B genetic loci would provide resistance to predominant races of loose smut found on the Canadian prairies.
The LOFAR Two-metre Sky Survey Shimwell, T. W.; Röttgering, H. J. A.; Best, P. N. ...
Astronomy and astrophysics (Berlin),
02/2017, Letnik:
598
Journal Article
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Odprti dostop
The LOFAR Two-metre Sky Survey (LoTSS) is a deep 120–168 MHz imaging survey that will eventually cover the entire northern sky. Each of the 3170 pointings will be observed for 8 h, which, at most ...declinations, is sufficient to produce ∼5 resolution images with a sensitivity of ∼100 µJy/beam and accomplish the main scientific aims of the survey, which are to explore the formation and evolution of massive black holes, galaxies, clusters of galaxies and large-scale structure. Owing to the compact core and long baselines of LOFAR, the images provide excellent sensitivity to both highly extended and compact emission. For legacy value, the data are archived at high spectral and time resolution to facilitate subarcsecond imaging and spectral line studies. In this paper we provide an overview of the LoTSS. We outline the survey strategy, the observational status, the current calibration techniques, a preliminary data release, and the anticipated scientific impact. The preliminary images that we have released were created using a fully automated but direction-independent calibration strategy and are significantly more sensitive than those produced by any existing large-area low-frequency survey. In excess of 44 000 sources are detected in the images that have a resolution of 25 , typical noise levels of less than 0.5 mJy/beam, and cover an area of over 350 square degrees in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45 • 00 00 to 57 • 00 00).
Plants produce a variety of proteinase inhibitors (PIs) that have a major function in defense against insect herbivores. In turn, insects have developed strategies to minimize the effect of dietary ...PIs on digestion. We have discovered that Helicoverpa larvae that survive consumption of a multidomain serine PI from Nicotiana alata (NaPI) contain high levels of a chymotrypsin that is not inhibited by NaPI. Here we describe the isolation of this NaPI-resistant chymotrypsin and an NaPI-susceptible chymotrypsin from Helicoverpa larvae, together with their corresponding cDNAs. We investigated the mechanism of resistance by mutating selected positions of the NaPI-susceptible chymotrypsin using the corresponding amino acids of the NaPI-resistant chymotrypsin. Four critical residues that conferred resistance to NaPI were identified. Molecular modeling revealed that a Phe→Leu substitution at position 37 in the chymotrypsin results in the loss of important binding contacts with NaPI. Identification of the molecular mechanisms that contribute to PI resistance in insect digestive proteases will enable us to develop better inhibitors for the control of lepidopteran species that are major agricultural pests worldwide.
The recovery of metastable structures formed at high pressure has been a long-standing goal in the field of condensed matter physics. While laser-driven compression has been used as a method to ...generate novel structures at high pressure, to date no high-pressure phases have been quenched to ambient conditions. Here we demonstrate, using in situ x-ray diffraction and recovery methods, the successful quench of a high-pressure phase which was formed under laser-driven shock compression. We show that tailoring the pressure release path from a shock-compressed state to eliminate sample spall, and therefore excess heating, increases the recovery yield of the high-pressure ω phase of zirconium from 0% to 48%. Our results have important implications for the quenchability of novel phases of matter demonstrated to occur at extreme pressures using nanosecond laser-driven compression.
Previous data suggest the existence of discrete pools of inositol lipids, which are components of a nuclear phosphoinositide (PI) cycle. However, it is not known whether the contents of these pools ...are regulated during cell proliferation. In the present study we demonstrate that the mass levels of three important constituents of the nuclear PI cycle are regulated during the cell cycle. Radioactive label incorporation into PtdIns(4,5)P(2) was seen to increase dramatically as synchronized cells entered S-phase. This did not coincide with any significant changes in the nuclear mass levels of this lipid, suggesting that the rate of turnover of this molecule was increased. Levels of PtdIns4P, the major substrate for PtdIns(4,5)P(2) production by Type I PtdInsP kinases (PIPkins), were regulated during the cell cycle and indicated a complex relationship between these two lipids. An alternative substrate for PtdIns(4,5)P(2), PtdIns5P, phosphorylated by Type II PIPkins, was present in nuclei at much smaller amounts than the PtdIns4P, and thus is unlikely to contribute significantly to PtdIns(4,5)P(2) turnover. However, a large increase in nuclear PtdIns5P mass was observed when murine erythroleukaemia cells are in G(1), and this could represent a potential pool of nuclear inositol lipid that has a specific signalling role. Analysis of extracted lipid fractions indicated the absence of any PtdIns3P in these nuclei.
Leptin can act as a satiety factor and exert neuroendocrine effects, but most studies have been performed in fasted animals. We aimed to determine the effect of chronic under-nutrition on the ...response to a 3-day intracerebroventricular infusion of leptin with regard to food intake and the secretion of pituitary hormones. Ovariectomised ewes (n=6) had a mean (+/-s.e.m. ) bodyweight of 56+/-0.8 kg on a diet available ad libitum (ad lib) or 33.4+/-1 kg on a restricted diet. The differential bodyweight was achieved by dietary means over a period of 6 months prior to the commencement of the study. Leptin (4 microg/h) or vehicle (artificial cerebrospinal fluid (aCSF)) was infused into the third cerebral ventricle for 3 days. Blood samples were taken prior to commencement and on day 3 of infusion for the assay of plasma hormone levels. The experiment was repeated one week later in a cross-over design. Food intake and metabolic status were monitored daily. The luteinising hormone (LH) pulse amplitude was lower (P<0.05) but plasma growth hormone (GH) levels were higher (P<0.05) in the food-restricted animals. Plasma levels of glucose, lactate, insulin, urea and triglycerides were similar in the two groups but non-esterified fatty acid levels were higher (P<0.01) in the animals on an ad lib diet. Leptin reduced (P<0.05) food intake only in the animals fed an ad lib diet. Leptin increased (P<0.05) the secretion of LH in the food-restricted group only and increased (P<0.05) GH irrespective of bodyweight. In conclusion, leptin does not alter food intake in animals on a restricted diet but can increase the secretion of LH in the same animals. The treatment of leptin was not sufficient to reduce plasma GH levels in the food-restricted animals, suggesting that other factors or mechanisms must be involved in the regulation of this axis.
The present report provides the first extensive characterization of the OT‐I TCR transgenic line, which produces MHC class I‐restricted, ovalbumin‐specific, CD8+ T cells (OT‐I cells). These cells are ...shown to be positively selected in vivo in H‐2b C57BL/6 mice and in bm5 mice, which express the Kbm5 mutant molecule. In contrast, OT‐I cells were not selected by mutant Kb molecules in bm1, bm3, bm8, bm10, bm11 or bm23 mice. Interestingly, however, when positive selection was examined in vitro in foetal thymic organ culture (FTOC), bm1 and bm8 were still poorly selective, but the bm3 haplotype now selected as efficiently as B6. The ability to select in vitro correlated with the capacity to present the ovalbumin (OVA) peptide to OT‐I cells, as measured by induction of an OVA‐specific proliferative response. These results suggest that a lower affinity TCR:MHC interaction may be necessary for positive selection in FTOC compared with selection in situ.
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