Biological activity of triazole fungicides towards Botrytis cinerea

Botrytis cinerea Pers. ex Fr., the causal agent of grey mould, is one of the most ubiquitous plant pathogens. The fungus is of high economic importance in various major crops and during transport and storage of agricultural products. Protectant fungicides such as chlorothalonil, dichlofluanid, folpet or thiram are widely used for disease control. Since their introduction in the 1960S/1970s, systemic fungicides such as the benzimidazoles or dicarboximides have been used extensively. However, their effectivity is severely hampered by a rapid development of resistance to these fungicides.Antifungal activity of N1-substituted azoles was discovered in the late 1960s. Since then, a large number of azole derivatives have been developed as agricultural fungicides and antimycotics. The mode of action of these azoles is based on inhibition of the cytochrome P450-dependent sterol 14α-demethylase (P450 14DM ), an enzyme of the sterol pathway. By now, sterol demethylation inhibitors (DMIs) comprise about 35 commercial products and represent the most important group of systemic fungicides. DMI fungicides are commonly applied in control of rusts, powdery mildews and scabs. Only few of them are registered for control of B. cinerea . This is ascribed to a limited field performance for which the reasons are not evident. A replacement of dicarboximides or benzimidazoles by DMI fungicides would be attractive, since DMIs have a number of advantages over other fungicides including a relatively low resistance risk.The aim of the study described in this thesis is to identify factors involved in the limited field performance of DMI fungicides towards B. cinerea . The study is restricted to the largest group of DMIs, the triazoles. Before presenting results obtained in this study a literature review on the biology and control of B. cinerea , the mode of action and mechanisms involved in selective fungitoxicity of DMI fungicides, and factors responsible for discrepancies in laboratory and field pesticide performance is given ( chapter 1 ). Biological activity of triazoles towards B. cinerea was investigated in vitro with cell-free assays ( chapters 3 - 4 ) and toxicity assays ( chapters 3 - 7) and in vivo on different hosts ( chapter 5 ).The first step in the research presented in this thesis was the development of a cell-free assay for sterol synthesis from the model fungus Penicillium italicum ( Moniliaceae ) according to a method described for Aspergillus fumigatus ( chapter 2 ). Subsequently, the method developed was adopted for Botrytis cinerea ( chapter 3). This assay was used to study the relationship between chemical structure and biological activity of commercial and experimental triazoles and stereoisomers of cyproconazole,SSF-109 and tebuconazole towards B. cinerea ( chapter 4 ). On basis of these experiments intrinsic inhibitory activity of triazoles towards P450 14DM of the target pathogen was determined. in following experiments, factors which influence In vivo activity or field performance were Investigated. In vivo activity of triazole fungicides towards B. cinerea was tested on foliar-sprayed tomato plants and diptreated grape berries, and compared with that of selected benzimidazoles and dicarboximides ( chapter 5 ). in this context was also studied whether biological compounds could specifically antagonize activity of triazoles ( chapter 5 ). Variation in triazole sensitivity of the pathogen population was studied for field isolates (121) of B. cinerea collected during 1970 - 1992 in Europe and israel ( chapter 6 ). in this survey less sensitive populations were detected. A putative mechanism of resistance to DMI fungicides in field isolates with a relatively low sensitivity to DMIs was studied and compared with that operating in laboratory-generated DMI-resistant mutants ( chapter 7 ). Effects of inhibitors of mitochondrial respiration and multisite-inhibiting fungicides on accumulation of tebuconazole were tested to evaluate their potency as candidate compounds in synergistic mixtures with DMIs ( chapter 7 ). The development of synergistic mixtures may improve biological activity of DMI fungicides in control of B. cinerea.</em

New records of Chondrichthycians species caught in the Cantabrian Sea (southern Bay of Biscay)

Seventeen chondrichthyan species were caught in the Cantabrian Sea (southern Bay of Biscay) during a multidisciplinary survey carried out in the Avile´s canyon system in May 2011. This survey provided the first records of three species (Galeus murinus, Neoraja iberica, and Neoraja caerulea) in these waters, and a further record of Rajella kukujevi. To confirm the identity of these species, the cytochrome c oxidase subunit I (COI) of the specimens was sequenced. Genetic analyses revealed that the DNA sequences of the two Neoraja species were identical in all the specimens analysed. Morphometric analyses, based on 40 characters, showed 3.66% dissimilarity between the two species. The morphometric character that contributed most to this discrepancy was disc width.Versión del editor1,023

Fermionic coherent states for pseudo-Hermitian two-level systems

We introduce creation and annihilation operators of pseudo-Hermitian fermions for two-level systems described by pseudo-Hermitian Hamiltonian with real eigenvalues. This allows the generalization of the fermionic coherent states approach to such systems. Pseudo-fermionic coherent states are constructed as eigenstates of two pseudo-fermion annihilation operators. These coherent states form a bi-normal and bi-overcomplete system, and their evolution governed by the pseudo-Hermitian Hamiltonian is temporally stable. In terms of the introduced pseudo-fermion operators the two-level system' Hamiltonian takes a factorized form similar to that of a harmonic oscillator.Comment: 13 pages (Latex, article class), no figures; v2: some amendments in section 2, seven new refs adde

Application of Pseudo-Hermitian Quantum Mechanics to a Complex Scattering Potential with Point Interactions

We present a generalization of the perturbative construction of the metric operator for non-Hermitian Hamiltonians with more than one perturbation parameter. We use this method to study the non-Hermitian scattering Hamiltonian: H=p^2/2m+\zeta_-\delta(x+a)+\zeta_+\delta(x-a), where \zeta_\pm and a are respectively complex and real parameters and \delta(x) is the Dirac delta function. For regions in the space of coupling constants \zeta_\pm where H is quasi-Hermitian and there are no complex bound states or spectral singularities, we construct a (positive-definite) metric operator \eta and the corresponding equivalent Hermitian Hamiltonian h. \eta turns out to be a (perturbatively) bounded operator for the cases that the imaginary part of the coupling constants have opposite sign, \Im(\zeta_+) = -\Im(\zeta_-). This in particular contains the PT-symmetric case: \zeta_+ = \zeta_-^*. We also calculate the energy expectation values for certain Gaussian wave packets to study the nonlocal nature of \rh or equivalently the non-Hermitian nature of \rH. We show that these physical quantities are not directly sensitive to the presence of PT-symmetry.Comment: 22 pages, 4 figure

Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion

Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt–Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt–Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt–Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt–Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk

The Importance of Biodiversity E-infrastructures for Megadiverse Countries

Addressing the challenges of biodiversity conservation and sustainable development requires global cooperation, support structures, and new governance models to integrate diverse initiatives and achieve massive, open exchange of data, tools, and technology. The traditional paradigm of sharing scientific knowledge through publications is not sufficient to meet contemporary demands that require not only the results but also data, knowledge, and skills to analyze the data. E-infrastructures are key in facilitating access to data and providing the framework for collaboration. Here we discuss the importance of e-infrastructures of public interest and the lack of long-term funding policies. We present the example of Brazil’s speciesLink network, an e-infrastructure that provides free and open access to biodiversity primary data and associated tools. SpeciesLink currently integrates 382 datasets from 135 national institutions and 13 institutions from abroad, openly sharing ~7.4 million records, 94% of which are associated to voucher specimens. Just as important as the data is the network of data providers and users. In 2014, more than 95% of its users were from Brazil, demonstrating the importance of local e-infrastructures in enabling and promoting local use of biodiversity data and knowledge. From the outset, speciesLink has been sustained through project-based funding, normally public grants for 2–4-year periods. In between projects, there are short-term crises in trying to keep the system operational, a fact that has also been observed in global biodiversity portals, as well as in social and physical sciences platforms and even in computing services portals. In the last decade, the open access movement propelled the development of many web platforms for sharing data. Adequate policies unfortunately did not follow the same tempo, and now many initiatives may perish

Spectral Singularities of a General Point Interaction

We study the problem of locating spectral singularities of a general complex point interaction with a support at a single point. We also determine the bound states, examine the special cases where the point interaction is P-, T-, and PT-symmetric, and explore the issue of the coalescence of spectral singularities and bound states.Comment: 11 page

Characterization of prion disease associated with a two-octapeptide repeat insertion

Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt–Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt–Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt–Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt–Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk

Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders

OBJECTIVE: People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. METHODS: We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other. RESULTS: Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. CONCLUSIONS: CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice

Stochastic pump effect and geometric phases in dissipative and stochastic systems

The success of Berry phases in quantum mechanics stimulated the study of similar phenomena in other areas of physics, including the theory of living cell locomotion and motion of patterns in nonlinear media. More recently, geometric phases have been applied to systems operating in a strongly stochastic environment, such as molecular motors. We discuss such geometric effects in purely classical dissipative stochastic systems and their role in the theory of the stochastic pump effect (SPE).Comment: Review. 35 pages. J. Phys. A: Math, Theor. (in press