A species-wide inventory of NLR genes and alleles in Arabidopsis thaliana

Infectious disease is both a major force of selection in nature and a prime cause of yield loss in agriculture. In plants, disease resistance is often conferred by nucleotide-binding leucine-rich repeat (NLR) proteins, intracellular immune receptors that recognize pathogen proteins and their effects on the host. Consistent with extensive balancing and positive selection, NLRs are encoded by one of the most variable gene families in plants, but the true extent of intraspecific NLR diversity has been unclear. Here, we define a nearly complete species-wide pan-NLRome in Arabidopsis thaliana based on sequence enrichment and long-read sequencing. The pan-NLRome largely saturates with approximately 40 well-chosen wild strains, with half of the pan-NLRome being present in most accessions. We chart NLR architectural diversity, identify new architectures, and quantify selective forces that act on specific NLRs and NLR domains. Our study provides a blueprint for defining pan-NLRomes

Strategic responses to global challenges: The case of European banking, 1973–2000

In applying a strategy, structure, ownership and performance (SSOP) framework to three major clearing banks (ABN AMRO, UBS, Barclays), this article debates whether the conclusions generated by Whittington and Mayer about European manufacturing industry can be applied to the financial services sector. While European integration plays a key role in determining strategy, it is clear that global factors were far more important in determining management actions, leading to significant differences in structural adaptation. The article also debates whether this has led to improved performance, given the problems experienced with both geographical dispersion and diversification, bringing into question the quality of decision-making over the long term

A survey of haptics in serious gaming

Serious gaming often requires high level of realism for training and learning purposes. Haptic technology has been proved to be useful in many applications with an additional perception modality complementary to the audio and the vision. It provides novel user experience to enhance the immersion of virtual reality with a physical control-layer. This survey focuses on the haptic technology and its applications in serious gaming. Several categories of related applications are listed and discussed in details, primarily on haptics acts as cognitive aux and main component in serious games design. We categorize haptic devices into tactile, force feedback and hybrid ones to suit different haptic interfaces, followed by description of common haptic gadgets in gaming. Haptic modeling methods, in particular, available SDKs or libraries either for commercial or academic usage, are summarized. We also analyze the existing research difficulties and technology bottleneck with haptics and foresee the future research directions

Blood volume measurement with indocyanine green pulse spectrophotometry: dose and site of dye administration

(1) To determine the optimal administration site and dose of indocyanine green (ICG) for blood volume measurement using pulse spectrophotometry, (2) to assess the variation in repeated blood volume measurements for patients after subarachnoid hemorrhage and (3) to evaluate the safety and efficacy of this technique in patients who were treated for an intracranial aneurysm. Four repeated measurements of blood volume (BV) were performed in random order of bolus dose (10 mg or 25 mg ICG) and venous administration site (peripheral or central) in eight patients admitted for treatment of an intracranial aneurysm. Another five patients with subarachnoid hemorrhage underwent three repeated BV measurements with 25 mg ICG at the same administration site to assess the coefficient of variation. The mean +/- SD in BV was 4.38 +/- 0.88 l (n = 25) and 4.69 +/- 1.11 l (n = 26) for 10 mg and 25 mg ICG, respectively. The mean +/- SD in BV was 4.59 +/- 1.15 l (n = 26) and 4.48 +/- 0.86 l (n = 25) for central and peripheral administration, respectively. No significant difference was found. The coefficient of variance of BV measurement with 25 mg of ICG was 7.5% (95% CI: 3-12%). There is no significant difference between intravenous administration of either 10 or 25 mg ICG, and this can be injected through either a peripheral or central venous catheter. The 7.5% coefficient of variation in BV measurements determines the detectable differences using ICG pulse spectrophotometr

Alcohol-related cerebellar degeneration: not all down to toxicity?

Background: Alcohol-related cerebellar degeneration is one of the commonest acquired forms of cerebellar ataxia. The exact pathogenic mechanisms by which alcohol leads to cerebellar damage remain unknown. Possible autoreactive immune mediated mechanisms have not been explored previously. In this study, we aim to investigate the potential role of alcohol-induced immune mediated cerebellar degeneration. Methods: Patients with ataxia and a history of alcohol misuse were recruited from the Ataxia and Hepatology tertiary clinics at Sheffield Teaching Hospitals NHS Trust. We determined the pattern of cerebellar involvement both on clinical (SARA score) and imaging (MRI volumetry and MR spectroscopy) parameters. In addition, HLA genotyping, serological markers for gluten-related disorders and serological reactivity on rat cerebellar tissue using indirect immunohistochemistry were assessed. Results: Thirty-eight patients were included in the study all of whom had ataxia. The gait (97 %), stance (89 %) and heel-shin slide (89 %) were the predominant SARA elements affected. MRI volumetric and spectroscopy techniques demonstrated significant structural, volumetric and functional deficits of the cerebellum with particular involvement of the cerebellar vermis. Circulating anti-gliadin antibodies were detected in 34 % patients vs. 12 % in healthy controls. Antibodies to transglutaminase 6 (TG6) were detected in 39 % of patients and 4 % of healthy control subjects. Using immunohistochemistry, Purkinje cell and/or granular layer reactivity was demonstrated in 71 % of patient sera. Conclusions: Alcohol induced tissue injury to the CNS leading to cerebellar degeneration may also involve immune mediated mechanisms, including sensitisation to gluten

Adult Patients with Congenital Adrenal Hyperplasia Have Elevated Blood Pressure but Otherwise a Normal Cardiovascular Risk Profile

Contains fulltext : 96615.pdf (publisher's version ) (Open Access)OBJECTIVE: Treatment with glucocorticoids and mineralocorticoids has changed congenital adrenal hyperplasia (CAH) from a fatal to a chronic lifelong disease. Long-term treatment, in particular the chronic (over-)treatment with glucocorticoids, may have an adverse effect on the cardiovascular risk profile in adult CAH patients. The objective of this study was to evaluate the cardiovascular risk profile of adult CAH patients. DESIGN: Case-control study. PATIENTS AND MEASUREMENTS: In this case-control study the cardiovascular risk profile of 27 adult CAH patients and 27 controls, matched for age, sex and body mass index was evaluated by measuring ambulatory 24-hour blood pressure, insulin sensitivity (HOMA-IR), lipid profiles, albuminuria and circulating cardiovascular risk markers (PAI-1, tPA, uPA, tPA/PAI-1 complex, hsCRP, adiponectin, IL-6, IL-18 and leptin). RESULTS: 24-Hour systolic (126.3 mmHg+/-15.5 vs 124.8 mmHg+/-15.1 in controls, P = 0.019) and diastolic (76.4 mmHg+/-12.7 vs 73.5 mmHg+/-12.4 in controls, P<0.001) blood pressure was significantly elevated in CAH patients compared to the control population. CAH patients had higher HDL cholesterol levels (P<0.01), lower hsCRP levels (P = 0.03) and there was a trend toward elevated adiponectin levels compared to controls. Other cardiovascular risk factors were similar in both groups. CONCLUSION: Adult CAH patients have higher ambulatory blood pressure compared to healthy matched controls. Other cardiovascular risk markers did not differ, while HDL-cholesterol, hsCRP and adiponectin levels tended to be more favorable

Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid Arthritis Synovial Fibroblasts

Galectin-9 (Gal9) has been postulated to have anti-infammatory properties based on the ability of exogenous Gal9 to induce apoptosis in synovial fbroblasts in animal models of rheumatoid arthritis (RA). Here we aimed to assess the potential role of endogenous Galectins, including Gal9, in the infammatory pathology of the RA synovium in humans. Firstly expression of Galectins 1–9 was determined in synovial fbroblasts (RASF) and dermal fbroblasts (DF) isolated from RA patients, the latter representing a non-infamed site. We then further challenged the cells with pro-infammatory TLR agonists and cytokines and assessed Galectin expression. Gal9 was found to be diferentially and abundantly expressed in RASF compared to DF. Agonists of TLR3 and TLR4, along with IFNgamma were also found to induce Gal9 expression in RASF. siRNA was then used to knock-down Gal9 expression in RASF and the efects of this on apoptosis and cell viability were assessed. Increased apoptosis was observed in RASF following Gal9 knock-down. We conclude that, unlike exogenous Gal9, endogenous Gal9 is protective against apoptosis and enhances synovial fbroblast viability suggesting that its role in RA is both pathogenic and pro-infammatory

Nosocomial Outbreak of Novel Arenavirus Infection, Southern Africa

This case reinforces the need for strict screening of internationally transferred patients

Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians

Copyright: Copyright 2008 Elsevier B.V., All rights reserved.The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.publishersversionPeer reviewe