An extracellular transglutaminase is required for apple pollen tube growth

An extracellular form of the calcium-dependent protein-crosslinking enzyme TGase (transglutaminase) was demonstrated to be involved in the apical growth of Malus domestica pollen tube. Apple pollen TGase and its substrates were co-localized within aggregates on the pollen tube surface, as determined by indirect immunofluorescence staining and the in situ cross-linking of fluorescently labelled substrates. TGase-specific inhibitors and an anti-TGase monoclonal antibody blocked pollen tube growth, whereas incorporation of a recombinant fluorescent mammalian TGase substrate (histidine-tagged green fluorescent protein:His6– Xpr–GFP) into the growing tube wall enhanced tube length and germination, consistent with a role of TGase as a modulator of cell wall building and strengthening. The secreted pollen TGase catalysed the cross-linking of both PAs (polyamines) into proteins (released by the pollen tube) and His6-Xpr-GFP into endogenous or exogenously added substrates. A similar distribution of TGase activitywas observed in planta on pollen tubes germinating inside the style, consistent with a possible additional role for TGase in the interaction between the pollen tube and the style during fertilization

Hypomorphic mutation in the RAG2 gene affects dendritic cell distribution and migration.

In Omenn syndrome, altered dendritic cell distribution and impaired migration represent an additional level of immune dysregulation, contributing to the pathogenesis of autoimmunity. OS is a severe combined immunodeficiency characterized by erythrodermia and protracted diarrhea as a result of infiltration of oligoclonal-activated T cells, caused by hypomorphic mutations in RAGs. The RAG2(R229Q) mouse model fully recapitulates the clinical OS phenotype. We evaluated whether T and B cell defects, together with the abnormal lymphoid structure, could affect DC homeostasis and function. High density of LCs was observed in skin biopsies of Omenn patients and in the derma of RAG2(R229Q) mice, correlating with the presence of erythrodermia. In vivo models of cutaneous skin painting and CHS demonstrated a decreased migration of RAG2(R229Q) DCsin particular, LCsinto draining LNs. Interestingly, at steady state, RAG2(R229Q) mice showed a reduction in DC number in all hematopoietic organs except LNs. Analysis of the MHCII marker revealed a diminished expression also upon the LPS-driven inflammatory condition. Despite the decreased number of peripheral DCs, BM pre-cDCs were present in normal number compared with RAG2(+/+) controls, whereas pDCs and monocytes were reduced significantly. Overall, these results point to a secondary defect in the DC compartment, which contributes to clinical manifestations and autoimmunity in OS

Allergic diseases in the elderly: biological characteristics and main immunological and non-immunological mechanisms

Life expectancy and the number of elderly people are progressively increasing around the world. Together with other pathologies, allergic diseases also show an increasing incidence in geriatric age. This is partly due to the growing emphasis on a more accurate and careful diagnosis of the molecular mechanisms that do not allow to ignore the real pathogenesis of many symptoms until now unknown, and partly to the fact that the allergic people from 20 years ago represent the elderly population now. Moreover, environmental pollution predisposes to the onset of allergic asthma and dermatitis which are the result of internal pathologies more than the expression of allergic manifestations. At the same time the food contamination permits the onset of allergic diseases related to food allergy. In this review we provide the state of the art on the physiological changes in the elderly responsible for allergic diseases, their biological characteristics and the major immunological and extra immunological mechanisms. Much emphasis is given to the management of several diseases in the elderly, including anaphylactic reactions. Moreover, some new features are discussed, such as management of asthma with the support of physical activity and the use of the AIT as prevention of respiratory diseases and for the purpose of a real and long lasting benefit. The mechanisms of adverse reactions to drugs are also discussed, due to their frequency in this age, especially in polytherapy regimens. Study of the modifications of the immune system is also of great importance, as regards to the distribution of the lymphocytes and also the presence of a chronic inflammatory disease related to the production of cytokines, especially in prevision of all the possible therapies to be adopted to allow an active and healthy agin

DADA: data assimilation for the detection and attribution of weather and climate-related events

A new nudging method for data assimilation, delay‐coordinate nudging, is presented. Delay‐coordinate nudging makes explicit use of present and past observations in the formulation of the forcing driving the model evolution at each time step. Numerical experiments with a low‐order chaotic system show that the new method systematically outperforms standard nudging in different model and observational scenarios, also when using an unoptimized formulation of the delay‐nudging coefficients. A connection between the optimal delay and the dominant Lyapunov exponent of the dynamics is found based on heuristic arguments and is confirmed by the numerical results, providing a guideline for the practical implementation of the algorithm. Delay‐coordinate nudging preserves the easiness of implementation, the intuitive functioning and the reduced computational cost of the standard nudging, making it a potential alternative especially in the field of seasonal‐to‐decadal predictions with large Earth system models that limit the use of more sophisticated data assimilation procedures

Left-right symmetry at LHC and precise 1-loop low energy data

Despite many tests, even the Minimal Manifest Left-Right Symmetric Model (MLRSM) has never been ultimately confirmed or falsified. LHC gives a new possibility to test directly the most conservative version of left-right symmetric models at so far not reachable energy scales. If we take into account precise limits on the model which come from low energy processes, like the muon decay, possible LHC signals are strongly limited through the correlations of parameters among heavy neutrinos, heavy gauge bosons and heavy Higgs particles. To illustrate the situation in the context of LHC, we consider the "golden" process $pp \to e^+ N$. For instance, in a case of degenerate heavy neutrinos and heavy Higgs masses at 15 TeV (in agreement with FCNC bounds) we get $\sigma(pp \to e^+ N)>10$ fb at $\sqrt{s}=14$ TeV which is consistent with muon decay data for a very limited $W_2$ masses in the range (3008 GeV, 3040 GeV). Without restrictions coming from the muon data, $W_2$ masses would be in the range (1.0 TeV, 3.5 TeV). Influence of heavy Higgs particles themselves on the considered LHC process is negligible (the same is true for the light, SM neutral Higgs scalar analog). In the paper decay modes of the right-handed heavy gauge bosons and heavy neutrinos are also discussed. Both scenarios with typical see-saw light-heavy neutrino mixings and the mixings which are independent of heavy neutrino masses are considered. In the second case heavy neutrino decays to the heavy charged gauge bosons not necessarily dominate over decay modes which include only light, SM-like particles.Comment: 16 pages, 10 figs, KL-KS and new ATLAS limits taken into accoun

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Supersymmetric contributions to Bˉs→ϕπ0\bar{B}_s \to \phi \pi^0 and Bˉs→ϕρ0\bar{B}_s \to \phi \rho^0 decays in SCET

We study the decay modes $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$ using Soft Collinear Effective Theory. Within Standard Model and including the error due to the SU(3) breaking effect in the SCET parameters we find that BR $\bar{B}_s\to \phi \pi^0 =7_{-1-2}^{+1+2}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \pi^0=9_{-1-4}^{+1+3}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively.For the decay mode $\bar{B}_s\to \phi \rho^0$, we find that BR $\bar{B}_s\to \phi \rho^0 = 20.2^{+1+9}_{-1-12}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \rho^0 = 34.0^{+1.5 + 15}_{-1.5-22}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively. We extend our study to include supersymmetric models with non-universal A-terms where the dominant contributions arise from diagrams mediated by gluino and chargino exchanges. We show that gluino contributions can not lead to an enhancement of the branching ratios of $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$. In addition, we show that SUSY contributions mediated by chargino exchange can enhance the branching ratio of $\bar{B}_s\to \phi \pi^0$ by about 14% with respect to the SM prediction. For the branching ratio of $\bar{B}_s\to \phi \rho^0$, we find that SUSY contributions can enhance its value by about 1% with respect to the SM prediction.Comment: 25 pages,5 figures, version accepted for publicatio

Low prevalence of significant carotid artery disease in Iranian patients undergoing elective coronary artery bypass

BACKGROUND: Coronary artery bypass grafting ranks as one of the most frequent operations worldwide. The presence of carotid artery stenosis may increase the stroke rate in the perioperative period. Routine preoperative noninvasive assessment of the carotid arteries are recommended in many institutions to reduce the stroke rate. METHODS: 271 consecutive patients undergoing coronary artery bypass grafting at Shaheed Madani hospital of Tabriz, Iran (age, 58.5 Y; 73.1% male) underwent preoperative ultrasonography for assessment of carotid artery wall thickness. RESULTS: Plaque in right common, left common, right internal and left internal carotid arteries was detected in 4.8%, 7.4%, 43.2% and 42.1% of patients respectively. 5 patients (1.8%) had significant (<50%) and 3 (1.1%) patients had critical (<70%) stenosis in internal carotid arteries. Plaque formation in common carotid was not significantly different between two genders but the stenosis of left internal carotid was more frequently seen among men. Patients with plaques in right or left internal carotid arteries were significantly older. CONCLUSION: Consecutive Iranian patients undergoing elective coronary artery bypass surgery show a very low prevalence of significant carotid artery disease

Predictive clinico-pathological factors to identify BCG, unresponsive patients, after re-resection for T1 high grade non-muscle invasive bladder cancer

Introduction: Seventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis. Materials and methods: Patients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients. Results: A total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05-1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22-2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02-1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P &lt; 0.0001) and at 10 years (44.2% vs. 74.4%, P &lt; 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P &lt; 0.0001) and at 10 years (72.3% vs. 87.2%, P &lt; 0.0001). Conclusion: Multifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes