First record of verticillium wilt (Verticillium longisporum) in winter oilseed rape in the UK

Verticillium longisporum is an important pathogen of oilseed rape (OSR) and vegetable brassicas in several European countries, but has not been reported previously in the UK (Karapapa et al., 1997; Steventon et al., 2002). In 2007, Verticillium wilt was suspected in UK crops of winter OSR (W-OSR) on cv. Castille in Romney Marsh, Kent and on cv. Barrel near Hereford. At these two locations, 32 and 10% of the plants, respectively, appeared to be affected, but the presence of stem canker may have masked some infections. Symptoms were first seen as the crops began to ripen (seeds green-brown to brown, Growth Stage: 6,4-6,5) and included brown and dark grey vertical bands on the stems from soil level into the branches, and premature ripening of some branches (Fig. 1). Microsclerotia were observed on stem samples collected in the field (Fig. 2), suggesting V. longisporum as the causal agent. Cultures were prepared from field samples by immersing stem pieces in 5% sodium hypochlorite solution for one minute, washing twice in sterile distilled water and plating onto potato dextrose agar containing 25 mg/l streptomycin sulphate. Isolates from three plants per outbreak were identified morphologically as V. longisporum. Mean conidial dimensions (25 spores per isolate) were 8.80-9.65 μm (length) and 2.50-2.85 μm (width) and all isolates produced elongated microsclerotia, characters typical of V. longisporum (Karapapa et al., 1997). The identity was confirmed by PCR using species-specific primers (Steventon et al., 2002) and, as a member of the α sub-group, by direct sequencing of the amplicons from primer pairs ITS4-ITS5 and DB19-DB22 (Collins et al., 2003; 2005). Sequences for isolate 003 from Kent were deposited in GenBank (Accession Nos. HQ702376 and HQ702377). All isolates tested from 2008 and 2009 were identical with previously deposited sequences for European OSR isolates (e.g. AF363992 and AF363246 respectively). Pathogenicity was confirmed by inoculating three OSR cv. Castille seedlings per isolate using the root dip technique with 1 x 106 spores/ml (Karapapa et al., 1997) under heated glasshouse conditions at 19°C. Leaf yellowing and blackening of the leaf veins were found 26 days after inoculation (Fig. 3). Yellowing affecting the three oldest leaves increased for seven to nine days. After five weeks the final mean leaf area affected was 63-78% with no differences between isolates. No leaf yellowing occurred in the controls. After five weeks, V. longisporum was re-isolated from all the inoculated seedlings, but not from the non-inoculated controls. In June 2008, infection of W-OSR crops in different fields on the same farms was found on cv. Es Astrid in Kent (56% incidence) and on cv. Lioness in Hereford (15% incidence). The Kent farm had been growing W-OSR alternating with winter wheat for at least 10 years whilst the Hereford farm had grown W-OSR one year in four. These short rotations of OSR may be contributing to the appearance of this disease. This study confirms the identification of V. longisporum on any host in the UK, through molecular studies and detailed spore measurements that were not reported in an earlier review (Gladders, 2009). This pathogen occurs in several European countries and, since OSR may be traded freely, following a Defra consultation, no statutory plant health action is to be taken

Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors

In the adult thymus, the development of self-tolerant thymocytes requires interactions with thymic epithelial cells (TECs). Although both cortical and medullary TECs (cTECs/mTECs) are known to arise from common bipotent TEC progenitors, the phenotype of these progenitors and the timing of the emergence of these distinct lineages remain unclear. Here, we have investigated the phenotype and developmental properties of bipotent TEC progenitors during cTEC/mTEC lineage development. We show that TEC progenitors can undergo a stepwise acquisition of first cTEC and then mTEC hallmarks, resulting in the emergence of a progenitor population simultaneously expressing the cTEC marker CD205 and the mTEC regulator Receptor Activator of NF-κB (RANK). In vivo analysis reveals the capacity of CD205(+) TECs to generate functionally competent cortical and medullary microenvironments containing both cTECs and Aire(+) mTECs. Thus, TEC development involves a stage in which bipotent progenitors can co-express hallmarks of the cTEC and mTEC lineages through sequential acquisition, arguing against a simple binary model in which both lineages diverge simultaneously from bipotent lineage negative TEC progenitors. Rather, our data reveal an unexpected overlap in the phenotypic properties of these bipotent TECs with their lineage-restricted counterparts

Surviving the Journey for Doctoral Students and Jr. Faculty: Panel Presentation and Discussion

Abbreviated presentations will be made by the four panelists that will focus on a range of topics of special interest to doctoral students and untenured junior faculty. The panelists’ presentations will serve as discussion starters for the session with the primary focus on the interaction among the conference attendees and the panelists

Lymphoid Tissue Inducer Cells: Pivotal Cells in the Evolution of CD4 Immunity and Tolerance?

Phylogeny suggests that the evolution of placentation in mammals was accompanied by substantial changes in the mammalian immune system: in particular lymph nodes and CD4 high affinity memory antibody responses co-evolved during the same period. Lymphoid tissue inducer cells (LTi) are members of an emerging family of innate lymphoid cells (ILCs) that are crucial for lymph node development, but our studies have indicated that they also play a pivotal role in the long-term maintenance of memory CD4 T cells in adult mammals through their expression of the tumor necrosis family members, OX40- and CD30-ligands. Additionally, our studies have shown that these two molecules are also key operators in CD4 effector function, as their absence obviates the need for the FoxP3 dependent regulatory T (Tregs) cells that prevent CD4 driven autoimmune responses. In this perspective article, we summarize findings from our group over the last 10 years, and focus specifically on the role of LTi in thymus. We suggest that like memory CD4 T cells, LTi also play a role in the selection and maintenance of the Tregs that under normal circumstances are absolutely required to regulate CD4 effector cells

Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, primarily affecting lower motor neurons. Recent evidence from SMA and related conditions suggests that glial cells can influence disease severity. Here, we investigated the role of glial cells in the peripheral nervous system by creating SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn(−/−);SMN2(tg/0);SMN1(SC)). Restoration of SMN protein levels restricted solely to Schwann cells reversed myelination defects, significantly improved neuromuscular function and ameliorated neuromuscular junction pathology in SMA mice. However, restoration of SMN in Schwann cells had no impact on motor neuron soma loss from the spinal cord or ongoing systemic and peripheral pathology. This study provides evidence for a defined, intrinsic contribution of glial cells to SMA disease pathogenesis and suggests that therapies designed to include Schwann cells in their target tissues are likely to be required in order to rescue myelination defects and associated disease symptoms

Prostate Surgery for Men with Lower Urinary Tract Symptoms: Do We Need Urodynamics to Find the Right Candidates?:Exploratory Findings from the UPSTREAM Trial

BackgroundIdentifying men whose lower urinary tract symptoms (LUTS) may benefit from surgery is challenging.ObjectiveTo identify routine diagnostic and urodynamic measures associated with treatment decision-making, and outcome, in exploratory analyses of the UPSTREAM trial.Design, setting, and participantsA randomised controlled trial was conducted including 820 men, considering surgery for LUTS, across 26 hospitals in England (ISCTRN56164274).InterventionMen were randomised to a routine care (RC) diagnostic pathway (n = 393) or a pathway that included urodynamics (UDS) in addition to RC (n = 427).Outcome measurements and statistical analysisMen underwent uroflowmetry and completed symptom questionnaires, at baseline and 18 mo after randomisation. Regression models identified baseline clinical and symptom measures that predicted recommendation for surgery and/or surgical outcome (measured by the International Prostate Symptom Score [IPSS]). We explored the association between UDS and surgical outcome in subgroups defined by routine measures.Results and limitationsThe recommendation for surgery could be predicted successfully in the RC and UDS groups (area under the receiver operating characteristic curve 0.78), with maximum flow rate (Qmax) and age predictors in both groups. Surgery was more beneficial in those with higher symptom scores (eg, IPSS >16), age 47.6, and bladder contractility index >123.0. In the UDS group, urodynamic measures were more strongly predictive of surgical outcome for those with Qmax >15, although patient-reported outcomes were also more predictive in this subgroup.ConclusionsTreatment decisions were informed with UDS, when available, but without evidence of change in the decisions reached. Despite the small group sizes, exploratory analyses suggest that selective use of UDS could detect obstructive pathology, missed by routine measures, in certain subgroups.Patient summaryBaseline clinical and symptom measurements were able to predict treatment decisions. The addition of urodynamic test results, while useful, did not generally lead to better surgical decisions and outcomes over routine tests alone

4-Phenylpyridin-2-one derivatives: a novel class of positive allosteric modulator of the M1 muscarinic acetylcholine receptor

Positive allosteric modulators (PAMs) of the M1 muscarinic acetylcholine receptor (M1 mAChR) are a promising strategy for the treatment of the cognitive deficits associated with diseases including Alzheimer’s and schizophrenia. Herein, we report the design, synthesis, and characterization of a novel family of M1 mAChR PAMs. The most active compounds of the 4-phenylpyridin-2-one series exhibited comparable binding affinity to the reference compound, 1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (BQCA) (1), but markedly improved positive cooperativity with acetylcholine, and retained exquisite selectivity for the M1 mAChR. Furthermore, our pharmacological characterization revealed ligands with a diverse range of activities, including modulators that displayed both high intrinsic efficacy and PAM activity, those that showed no detectable agonism but robust PAM activity and ligands that displayed robust allosteric agonism but little modulatory activity. Thus, the 4-phenylpyridin-2-one scaffold offers an attractive starting point for further lead optimization

An air-stable DPP-thieno-TTF copolymer for single-material solar cell devices and field effect transistors

Following an approach developed in our group to incorporate tetrathiafulvalene (TTF) units into conjugated polymeric systems, we have studied a low band gap polymer incorporating TTF as a donor component. This polymer is based on a fused thieno-TTF unit that enables the direct incorporation of the TTF unit into the polymer, and a second comonomer based on the diketopyrrolopyrrole (DPP) molecule. These units represent a donor–acceptor copolymer system, p(DPP-TTF), showing strong absorption in the UV–visible region of the spectrum. An optimized p(DPP-TTF) polymer organic field effect transistor and a single material organic solar cell device showed excellent performance with a hole mobility of up to 5.3 × 10–2 cm2/(V s) and a power conversion efficiency (PCE) of 0.3%, respectively. Bulk heterojunction organic photovoltaic devices of p(DPP-TTF) blended with phenyl-C71-butyric acid methyl ester (PC71BM) exhibited a PCE of 1.8%

Redesign and initial validation of an instrument to assess the motivational qualities of music in exercise: The Brunel Music Rating Inventory-2

In the present study, a measure to assess the motivational qualities of music in exercise was redesigned, extending previous research efforts (Karageorghis et al., 1999). The original measure, the Brunel Music Rating Inventory (BMRI), had shown limitations in its factor structure and its applicability to non-experts in music selection. Redesign of the BMRI used in-depth interviews with eight participants (mean age 31.9 years, s¼8.9 years) to establish the initial item pool, which was examined using a series of confirmatory factor analyses. A single-factor model provided a good fit across three musical selections with different motivational qualities (comparative fit index, CFI: 0.95 – 0.98; standardized root mean residual, SRMR: 0.03 – 0.05). The single-factor model also demonstrated acceptable fit across two independent samples and both sexes using one piece of music (CFI: 0.86 – 1.00; SRMR: 0.04 – 0.07). The BMRI was designed for experts in selecting music for exercise (e.g. dance aerobic instructors), whereas the BMRI-2 can be used both by exercise instructors and participants. The psychometric properties of the BMRI-2 are stronger than those of the BMRI and it is easier to use. The BMRI-2 provides a valid and internally consistent tool by which music can be selected to accompany a bout of exercise or a training session. Furthermore, the BMRI-2 enables researchers to standardize music in experimental protocols involving exercise-related tasks

A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5).

AIM: To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) vs insulin aspart (IAsp) used in continuous subcutaneous insulin infusion (CSII) in participants with type 1 diabetes (T1D). MATERIALS AND METHODS: This was a double-blind, treat-to-target, randomized, 16-week trial investigating CSII treatment with faster aspart (n = 236) or IAsp (n = 236). All available information, regardless of treatment discontinuation, was used for the evaluation of effect. RESULTS: Faster aspart was non-inferior to IAsp regarding the change from baseline in glycated haemoglobin (HbA1c; primary endpoint). The mean HbA1c changed from 58.4 mmol/mol (7.5%) at baseline to 57.8 mmol/mol (7.4%) with faster aspart and to 56.8 mmol/mol (7.4%) with IAsp after 16 weeks' treatment, with an estimated treatment difference (ETD) of 1.0 mmol/mol (95% confidence interval [CI] 0.14; 1.87) or 0.09% (95% CI 0.01; 0.17; P < 0.001) for non-inferiority (0.4% margin; P < 0.02 for statistical significance in favour of IAsp). Faster aspart was superior to IAsp in change from baseline in 1-hour postprandial glucose (PPG) increment after a meal test (ETD -0.91 mmol/L [95% CI -1.43; -0.39] or -16.4 mg/dL [95% CI -25.7; -7.0]; P = 0.001), with statistically significant reductions also at 30 minutes and 2 hours. The improvement in PPG was reflected in the change from baseline in 1-hour interstitial glucose increment after all meals (ETD -0.21 mmol/L [95% CI -0.31; -0.11] or -3.77 mg/dL [95% CI -5.53; -2.01]). There was no statistically significant difference in the overall rate of severe or blood glucose-confirmed hypoglycaemia (estimated rate ratio 1.00 [95% CI 0.85; 1.16]). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and 4-week run-in periods (4 vs 0). CONCLUSIONS: Faster aspart provides an effective and safe option for CSII treatment in T1D.NovoNordis