Factors affecting mycotoxin production by Fusarium species

Studies were undertaken to investigate the factors affecting mycotoxin production in Fusarium phytopatliogens. The conclusions of this work are divided into the following categories.Substantive findings:Contamination of cereal grains with Fusarium mycotoxins is a global and continuing issue and is likely to remain so until a systematic elucidation of controlling factors has been accomplished.An important observation at the commencement of the research programme examined the validity of using direct TLC analysis of agar culture plugs to establish mycotoxin profiles in Fusarium species.The results in this thesis indicate that this method only detected a limited number of mycotoxins and this was not consistent between surfaces of the plugs tested or between experiments in the preliminary series.A noteworthy observation was that HT-2 toxin production from T-2 toxin was not time- related as claimed by other workers. There may be a real species differences in this respect between F. sporotrichioides and F. poae.Mixtures of carbendazim and propiconazole or carbendazim plus maneb or carbendazim plus maneb plus tridemorph all enhanced T-2 toxin formation.The fungicide-induced enhancement of mycotoxin production has now been extended, for the first time, to HT-2 toxin and NEO.A substantive finding, not previously noted, is that difenoconazole failed to stimulate T-2 toxin formation at 25°C but was capable of transforming it to HT-2 toxin and then stimulating the production of the latter product.Difenoconazole appears to be a fungicide in a class of its own in that DAS and NEO production are consistently higher than for a large majority of other fungicides tested.NEO production was not substantially affected by fungal exposure to Bavistin, whereas carbendazim acted in a stimulatory manner. It is suggested that this discrepancy is due to fungicide form, an effect not previously reported.A novel finding has been a consistent indication of reduced efficacy of pesticides for the control of ZEN in the 25-11°C regime compared to the constant incubation at 25°C.The effects of incubation temperature on T-2 toxin production is dependent upon fungicide type whereas in the case of HT-2 toxin, DAS and NEO, there is a clear effect of temperature. Contrasting effects were observed in fungicide efficacy for the control of HT-2 toxin in the two temperature regimes. At 25°C, stimulation occurred at the 100 pig/inl dose but in the 25- 11°C regime, HT-2 toxin production was almost eliminated at the same concentration.It is suggested that the complex interactions involving fungicides, temperature and duration of exposure to these factors may be critical in the timing of fungicide applications in the field.A new classification for fungicide efficacy is proposed, based on the capacity to completely control FHB/grain infection/fungal growth and mycotoxin production on grain or in culture. Three classes have been identified. Most fungicides appear in the Class III group, incorporating fungicides that are either ineffective or capable of stimulating trichothecene production.Although maneb has been identified as a Class I fungicide from evidence in the literature, its high efficacy is not conferred to mixtures incorporating this fungicide.A novel finding in the present study with F. culmorum was the demonstration of 3-ADON enhancement induced by the herbicide combination of bromoxynil, ioxynil and mecoprop added as Swipe.A radical re-design of pesticides is proposed to incorporate efficacy for regulation of mycotoxin biosynthesis.Secondary findings:A rule-of-thumb based on colour differences of Fusarium colonies is proposed. The present results suggest that the striking differences in pigmentation might be associated with the pattern of mycotoxin production. Thus yellow is possibly indicative of the presence of T-2 toxin, HT-2 toxin, DON, 15-ADON and 3-ADON while pink/red coloration might suggest the production of ZEN. This rule-of-thumb, if sufficiently developed, might find application in field assessments of toxigenic potential in cases of cereal diseases such as FHB.The lack of efficacy of propiconazole to regulate trichothecene production has been extended to instances where it is combined with other fungicides.Confirmatory findings:Present results with F. sporotrichioides confirm for only the second time in recent years that this phytopathogen is a consistent producer of ZEN.Biosynthesis of ZEN is clearly temperature-sensitive but there may be species differences regarding this effect.The enhancement effect of fungicides on T-2 toxin production has now been extended to carbendazim.New hypothesis:The current studies on gene expression indicate future potential for elucidating the biochemical mechanisms underlying trichothecene biosynthesis as affected by factors such as incubation temperature and fungicide applications. Such an approach might lead to more effective pesticides

Motor-driven Dynamics of Cytoskeletal FIlaments in Motility Assays

We model analytically the dynamics of a cytoskeletal filament in a motility assay. The filament is described as rigid rod free to slide in two dimensions. The motor proteins consist of polymeric tails tethered to the plane and modeled as linear springs and motor heads that bind to the filament. As in related models of rigid and soft two-state motors, the binding/unbinding dynamics of the motor heads and the dependence of the transition rates on the load exerted by the motor tails play a crucial role in controlling the filament's dynamics. Our work shows that the filament effectively behaves as a self-propelled rod at long times, but with non-Markovian noise sources arising from the coupling to the motor binding/unbinding dynamics. The effective propulsion force of the filament and the active renormalization of the various friction and diffusion constants are calculated in terms of microscopic motor and filament parameters. These quantities could be probed by optical force microscopy.Comment: 13 pages, 8 figures, 1 Tabl

In vitro and in vivo targeting of different folate receptor-positive cancer cell lines with a novel 99mTc-radiofolate tracer

Purpose: For the assessment of folate-based radiopharmaceuticals, human nasopharyngeal KB carcinoma cells are traditionally used although nasopharyngeal cancer is rare. On the other hand, the folate receptor (FR) is frequently overexpressed on diverse cancer types, the highest frequency (>90%) being on ovarian carcinomas. The goal of our study was the in vitro and in vivo assessment of different FR-positive human carcinoma cells. In addition, a murine sarcoma cell line was assessed as a pre-clinical alternative to human xenograft models. Methods: FR-positive human nasopharyngeal, cervical, ovarian and colorectal cancer cell lines and the transgenic mouse sarcoma (24JK-FBP) cell line were targeted with a novel 99mTc-tricarbonyl folate derivative 2. Comparative in vitro cell binding studies were carried out under standardised folate-deficient conditions. In vivo studies were performed in nude mice and C6 black mice. Results: The in vitro cell experiments revealed only FR-specific binding (unspecific <0.02%), ranging from 3.5% to 52% of complex 2 owing to variable levels of FR expression of the cell lines. In vivo tumour uptake of radiotracer 2 varied less than in vitro. It ranged from 0.66±0.17% ID/g (LoVo) through 1.16±0.64%ID/g (IGROV-1) and 1.55±0.43% ID/g (24JK-FBP) to 2.33±0.36% ID/g (KB) 4h p.i. Conclusion: These pre-clinical studies indicate that in vitro data obtained in FR-positive cancer cells do not necessarily correspond with or predict in vivo radiofolate uptake in corresponding (xeno)grafts. In addition, the murine 24JK-FBP cell line proved to be a valuable pre-clinical alternative to human tumour model

Quantum Pattern Retrieval by Qubit Networks with Hebb Interactions

Qubit networks with long-range interactions inspired by the Hebb rule can be used as quantum associative memories. Starting from a uniform superposition, the unitary evolution generated by these interactions drives the network through a quantum phase transition at a critical computation time, after which ferromagnetic order guarantees that a measurement retrieves the stored memory. The maximum memory capacity p of these qubit networks is reached at a memory density p/n=1.Comment: To appear in Physical Review Letter

Preclinical evaluation of novel organometallic 99mTc-folate and 99mTc-pteroate radiotracers for folate receptor-positive tumour targeting

Purpose: The folate receptor (FR) is a valuable tumour marker, since it is frequently overexpressed on various cancer types. The purpose of the present study was to pre-clinically evaluate novel site-specifically modified 99mTc(CO)3 folate (γ-derivative 4, α-derivative 5) and pteroate (6) conjugates for FR targeting. Methods: The 99mTc(CO)3 radiotracers 4-6 were prepared by a kit-like procedure. In vitro characterisation (K D and B max) of the radiotracers was performed with FR-positive KB cells. Tissue distribution was studied in tumour-bearing mice. SPECT/CT experiments were performed with a dedicated small animal SPECT/CT scanner. Results: The complexes 4-6 were formed in high yields (>92%). Binding constants of the radiotracers (K D in nM: 4: 2.09; 5: 2.51; 6: 14.52) were similar to those of 3H-folic acid (K D in nM: 7.22). In vivo the folate derivatives showed significantly better tumour uptake (4: 2.3±0.4% ID/g and 5: 1.2±0.2% ID/g, 4h p.i.) than the pteroate derivative (6: 0.4±0.2% ID/g, 4h p.i.). Clearance of all radiotracers from the blood pool and from non-targeted tissues was efficient (tumour to blood ratio approx. 200-350, 24h p.i.). FR-positive tissue and organs were successfully visualised via small animal SPECT/CT. Conclusion: Radiotracers 4-6 are the first 99mTc(CO)3 tracers prepared via a kit formulation which exhibit full biological activity in vitro and in vivo. Folate derivatives 4 and 5 revealed significantly better pharmacokinetic properties than the pteroate derivative 6. Promising pre-clinical SPECT results warrant further assessment of 99mTc(CO)3 radiofolates for detection of FR-positive tumour

Key Intermediates: A simple and Highly Selective Synthesis of 5-amino-1-aryl-1H-pyrazole-4-carbonitriles for Applications in the Crop Protection

A series of six pyrazoles was synthesized by Michael-type addition reaction. The molecules 5- amino-1-aryl-1H-pyrazole-4-carbonitrile (3a-f) were synthesized from (ethoxymethylene)malononitrile (1) and fluorinated and non-fluorinated aryl hydrazines (2a-f) using ethanol and fluorinated ethanol as solvents at reflux. An excellent regio-selectivity was found when pyrazole derivatives were formed as an exclusive product. No other regioisomer or uncyclised hydrazide was observed. Their structures were confirmed by spectroscopy data (1H, 13C, 19F, COSY (correlation spectroscopy), HSQC (heteronuclear single-quantum correlation spectroscopy) and HMBC (heteronuclear multiple-bond correlation spectroscopy); MS (mass-spectrometry). The yields ranged from good to excellent (47% - 93%) under mild reaction conditions. It would indicate a high selectivity in the one-step work procedure. These products (3a-f) and derivatives have a potential academic and industrial use as key intermediates, in special, for application in crop protection.Fil: Plem, Silvana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Müller, Diana. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Motor development in the hospitalized infant and its biological and environmental characteristics

Introduction: Hospitalization is a risk factor for delayed motor development, due to the lack of adequate stimulation; therefore, it is important to assess child development during hospital admission.Methods: In this study, motor development of previously healthy hospitalized infants was assessed and associated with biological and environmental characteristics, including length of hospital stay and physiotherapeutic treatment. The assessment was made before discharge, with questionnaires and a motor assessment scale.Results: The sample of 32 infants aged from zero to 18 months had an average length of hospital stay of 4.94±2.39 days. 50% of infants were girls (n = 16) and mostly belonged to socioeconomic class C (n = 16). Length of hospital stay explained only 3.3% of motor development variation, showing no significant impact. Infants from lower socioeconomic classes were nearly six times more susceptible to motor delays than those belonging to higher classes (p = 0.05). During hospitalization, 25% of the sample (n = 8) was treated with physiotherapy. All these patients were hospitalized for respiratory dysfunction and presented five times less chance of altered motor development when compared to those who did not undergo physiotherapy.Conclusion: These results should be interpreted with caution, since the type of physiotherapy care provided and infant’s degree of motor impairment were unknown. In this study, length of stay and hospital environment were not significant risk factors when analyzed individually, concluding that the greater the exposure and the amount of associated factors, the more susceptible the infant will be to present motor delays.Keywords: Child development; hospitalization; developmental disabilities Introduction: Hospitalization is a risk factor for delayed motor development, due to the lack of adequate stimulation; therefore, it is important to assess child development during hospital admission. Methods: In this study, motor development of previously healthy hospitalized infants was assessed and associated with biological and environmental characteristics, including length of hospital stay and physiotherapeutic treatment. The assessment was made before discharge, with questionnaires and a motor assessment scale. Results: The sample of 32 infants aged from zero to 18 months had an average length of hospital stay of 4.94 ± 2.39 days. 50% of infants were girls (n = 16) and mostly belonged to socioeconomic class C (n = 16). Length of hospital stay explained only 3.3% of motor development variation, showing no significant impact. Infants from lower socioeconomic classes were nearly six times more susceptible to motor delays than those belonging to higher classes (p = 0.05). During hospitalization, 25% of the sample (n = 8) was treated with physiotherapy. All these patients were hospitalized for respiratory dysfunction and presented five times less chance of altered motor development when compared to those who did not undergo physiotherapy. Conclusion: These results should be interpreted with caution, since the type of physiotherapy care provided and infant’s degree of motor impairment were unknown. In this study, length of stay and hospital environment were not significant risk factors when analyzed individually, concluding that the greater the exposure and the amount of associated factors, the more susceptible the infant will be to present motor delays.Keywords: Child development; hospitalization; developmental disabilities 

Rhétorique de l’ingenium et personnalité littéraire

The purpose of this study is to briefly outline the historical evolution of the ingenium in the premodern culture. A rhetorical and literary concept, the ingenium organizes the ancient notion of the capacity of invention and of artistic inspiration, and eventually becomes a central concept in the classic Aesthetic thought. But its meaning and evolution are also intimately related to the discovery of the individuality, and to the tension between natura (the natural, inborn characteristics) and ars, doctrina (acquired, secondary, elaborated characteristics of an individual style). From Plato and Aristotle, through Cicero, Quintilian and Erasmus, the classic Aesthetics articulates a question still meaningful for the modern reflection on the individual : how can the tension between the acknowledged diversity of ingenia and the necessity for a unifying discipline like Rhetorics be ultimately reduced.No disponible en español

Evaluation of a novel radiofolate in tumour-bearing mice: promising prospects for folate-based radionuclide therapy

Purpose: Folate-based radiopharmaceuticals have the potential to be used for imaging and therapy of tumours positive for the folate receptor (FR). We describe the in vitro and in vivo evaluation of a DOTA-folate conjugate. Methods: Radiolabelling of the DOTA-folate was carried out via standard procedures using 111InCl3 and 177LuCl3, respectively. The distribution coefficient (log D) was determined in octanol/PBS (pH 7.4). Tissue distribution was investigated in nude mice bearing KB tumour xenografts at different time points after administration of 111In-DOTA-folate (radiofolate 1) or 177Lu-DOTA-folate (radiofolate 2) (1MBq, 1nmol per mouse). Pemetrexed (PMX, 400μg) was injected 1h prior to the radiofolate in order to reduce renal uptake. Images were acquired with a SPECT/CT camera 24h after injection of the radiofolate (40-50MBq, 3nmol per mouse). Results: The hydrophilic character of the DOTA-folate was represented by a low log D value (radiofolate 1 −4.21±0.11). In vivo, maximal tumour uptake was found 4h after injection (radiofolate 1 5.80±0.55%ID/g; radiofolate 2 7.51±1.25%ID/g). In FR-positive kidneys there was considerable accumulation of the radiofolates (radiofolate 1 55.88±3.91%ID/g; radiofolate 2 57.22±11.05%ID/g; 4h after injection). However, renal uptake was reduced by preinjection of PMX (radiofolate 1 9.52±1.07%ID/g; radiofolate 2 13.43±0.54%ID/g; 4h after injection) whereas the tumour uptake was retained (radiofolate 1 6.32±0.41%ID/g; radiofolate 2 8.99±0.43%ID/g; 4h after injection). SPECT/CT images clearly confirmed favourable tissue distribution of the novel radiofolates and the positive effect of PMX. Conclusion: The preliminary requirements for the therapeutic use of the novel DOTA-folate are met by its favourable tissue distribution that can be ascribed to its hydrophilic properties and combined administration with PM