Off-line learning in a rhythmic bimanual task: early feedback dependency is reduced over wakefulness.

Research has supported two distinct forms of motor skill consolidation that can occur between practice sessions: (1) off-line learning, and (2) memory stabilization. Off-line learning describes performance improvement between practice sessions that is above the gain observed at the end of practice, while memory stabilization describes a gain in performance that is maintained between practice sessions. This study used a Lissajous plot to provide concurrent feedback to train participants to produce a 90° relative phase between the index fingers (flexion/extension motion). Significant improvements in performance emerged after ten trials (5 min) of practice. At the end of training, participants were divided into two delay interval groups before retesting, 2-h and 6-h. The retesting session started with participants performing an interference task (10 trials, 5 min) that required training on a 45° relative phase between the fingers with concurrent feedback from the Lissajous plot. When training with the interference task was completed participants were retested with the 90° relative phase without the Lissajous plot feedback. In the retest of the 90° pattern, a performance loss was found in the 2-h delay group, whereas the 6-h delay group maintained the end of practice performance level. Maintenance of the same level of performance without the Lissajous plot represents memory stabilization of the initially trained 90° pattern. The findings are discussed within the context of current positions regarding procedural consolidation and the coordination dynamics framework wherein action and perception are linked through the informational nature of relative phase.

Structure-Guided In Vitro to In Vivo Pharmacokinetic Optimization of Propargyl-Linked Antifolates.

Pharmacokinetic/pharmacodynamic properties are strongly correlated with the in vivo efficacy of antibiotics. Propargyl-linked antifolates, a novel class of antibiotics, demonstrate potent antibacterial activity against both Gram-positive and Gram-negative pathogenic bacteria, including multidrug-resistant Staphylococcus aureus Here, we report our efforts to optimize the pharmacokinetic profile of this class to best match the established pharmacodynamic properties. High-resolution crystal structures were used in combination with in vitro pharmacokinetic models to design compounds that not only are metabolically stable in vivo but also retain potent antibacterial activity. The initial lead compound was prone to both N-oxidation and demethylation, which resulted in an abbreviated in vivo half-life (∼20 minutes) in mice. Stability of leads toward mouse liver microsomes was primarily used to guide medicinal chemistry efforts so robust efficacy could be demonstrated in a mouse disease model. Structure-based drug design guided mitigation of N-oxide formation through substitutions of sterically demanding groups adjacent to the pyridyl nitrogen. Additionally, deuterium and fluorine substitutions were evaluated for their effect on the rate of oxidative demethylation. The resulting compound was characterized and demonstrated to have a low projected clearance in humans with limited potential for drug-drug interactions as predicted by cytochrome P450 inhibition as well as an in vivo exposure profile that optimizes the potential for bactericidal activity, highlighting how structural data, merged with substitutions to introduce metabolic stability, are a powerful approach to drug design.

The protective effects of acute cardiovascular exercise on the interference of procedural memory.

Numerous studies have reported a positive impact of acute exercise for procedural skill memory. Previous work has revealed this effect, but these findings are confounded by a potential contribution of a night of sleep to the reported exercise-mediated reduction in interference. Thus, it remains unclear if exposure to a brief bout of exercise can provide protection to a newly acquired motor memory. The primary objective of the present study was to examine if a single bout of moderate-intensity cardiovascular exercise after practice of a novel motor sequence reduces the susceptibility to retroactive interference. To address this shortcoming, 17 individuals in a control condition practiced a novel motor sequence that was followed by test after a 6-h wake-filled interval. A separate group of 17 individuals experienced practice with an interfering motor sequence 45 min after practice with the original sequence and were then administered test trials 6 h later. One additional group of 12 participants was exposed to an acute bout of exercise immediately after practice with the original motor sequence but prior to practice with the interfering motor sequence and the subsequent test. In comparison with the control condition, increased response times were revealed during the 6-h test for the individuals that were exposed to interference. The introduction of an acute bout of exercise between the practice of the two motor sequences produced a reduction in interference from practice with the second task at the time of test, however, this effect was not statistically significant. These data reinforce the hypothesis that while there may be a contribution from exercise to post-practice consolidation of procedural skills which is independent of sleep, sleep may interact with exercise to strengthen the effects of the latter on procedural memory.

Dairy intake in relation to in vitro fertilization outcomes among women from a fertility clinic.

STUDY QUESTION: Is dairy food consumption associated with live birth among women undergoing infertility treatment? SUMMARY ANSWER: There was a positive association between total dairy food consumption and live birth among women ≥35 years of age. WHAT IS KNOWN ALREADY: Dairy food intake has been previously related to infertility risk and measures of fertility potential but its relation to infertility treatment outcomes are unknown. STUDY DESIGN, SIZE, DURATION: Our study population comprised a total of 232 women undergoing 353 in vitro fertilization (IVF) treatment cycles between February 2007 and May 2013, from the Environment and Reproductive Health study, an ongoing prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diet was assessed before assisted reproductive technology (ART) treatment using a validated food frequency questionnaire. Study outcomes included ovarian stimulation outcomes (endometrial thickness, estradiol levels and oocyte yield), fertilization rates, embryo quality measures and clinical outcomes (implantation, clinical pregnancy and live birth rates). We used generalized linear mixed models with random intercepts to account for multiple ART cycles per woman while simultaneously adjusting for age, caloric intake, BMI, race, smoking status, infertility diagnosis, protocol type, alcohol intake and dietary patterns. MAIN RESULTS AND THE ROLE OF CHANCE: The age- and calorie-adjusted difference in live birth between women in the highest (>3.0 servings/day) and lowest (<1.34 servings/day) quartile of dairy intake was 21% (P = 0.02). However, after adjusting for additional covariates, this association was observed only among women ≥35 years (P, interaction = 0.04). The multivariable-adjusted live birth (95% CI) in increasing quartiles of total dairy intake was 23% (11, 42%), 39% (24, 56%), 29% (17, 47%) and 55% (39, 69%) (P, trend = 0.02) among women ≥35 years old, and ranged from 46 to 54% among women <35 years old (P, trend = 0.69). There was no association between dairy intake and any of the intermediate outcomes. LIMITATIONS, REASONS FOR CAUTION: The lack of a known biological mechanism linking dairy intake to infertility treatment outcomes calls for caution when interpreting these results and for additional work to corroborate or refute them. WIDER IMPLICATIONS OF THE FINDINGS: Dairy intake does not appear to harm IVF outcomes and, if anything, is associated with higher chances of live birth. STUDY FUNDING/COMPETING INTERESTS: This work was supported by NIH grants R01-ES009718 and R01ES000002 from NIEHS, P30 DK046200 from NIDDK and T32HD060454 from NICHD. M.C.A. was supported by a Ruth L. Kirschstein National Research Service Award T32 DK 007703-16 from NIDDK. She is currently employed at the Nestlé Research Center, Switzerland and completed this work while at the Harvard School of Public Health. The other authors declare no conflicts of interest.

First Report of Phakopsora pachyrhizi Adapting to Soybean Genotypes with Rpp1 or Rpp6 Rust Resistance Genes in Field Plots in the United States.

During the years following the first detection of soybean rust, caused by Phakopsora pachyrhizi Syd., in the continental United States in November, 2004, soybean (Glycine max [L.] Merr.) genotypes with the Rpp1 or Rpp6 resistance genes exhibited high levels of resistance there (1,2,3). When challenged with 72 different American isolates collected between 2006 and 2009, PI 200492 (source of Rpp1) produced no sporulating lesions (2). In 2011 and 2012, however, field populations of P. pachyrhizi from Gadsden County, FL, caused higher rust severity on plants with Rpp1 or Rpp6 than in previous years. To assess aggressiveness, sporulation ratings were made using a 1 to 5 scale (no sporulation to profuse sporulation) on leaflets collected from field plants at or near the R6 (full seed) stage of development. A dissecting microscope was used to examine 3 replications of 5 leaflets each in 2009 or 2 replications of 10 leaflets each in 2012. The sporulation ratings increased on PI 200492 (from 1.1 ± 0.1 in 2009 to 4.1 ± 0.4 in 2012), PI 567102B (Rpp6; from 1.1 ± 0.1 in 2009 to 2.4 ± 0.2 in 2012), and L85-2378, a 'Williams 82' isoline carrying the Rpp1 gene (from 1.0 ± 0 in 2009 to 4.0 ± 0.3 in 2012). The mean 2009 and 2012 sporulation ratings for susceptible control Williams 82 were 5.0 ± 0 and 4.2 ± 0.1, respectively. Single-uredinium-derived isolates were purified from bulk isolates collected from field plots in 2009 (FL-Q09-1), 2011 (FL-Q11-1), and 2012 (FL-Q12-1). Greenhouse and detached leaflet assays were then used to test the virulence of these isolates under controlled conditions. Detached leaflets from 3-week-old seedlings of Williams 82, PI 200492, PI 567102B, and L85-2378 were inoculated by pipetting 15-µl drops of a 30 to 40 urediniospore µl-1 suspension onto the abaxial side of 3 to 4 leaflets per genotype, which were then sealed in Petri plates and incubated in a growth chamber at 20 to 22°C. Plates were kept in the dark for 12 h following inoculation. For the greenhouse assay, the first trifoliolate leaves of at least 3 seedlings were each sprayed with 1.5 ml of a 40 urediniospore µl-1 suspension and incubated 24 h at 22 to 24°C in a dark mist chamber. The plants were then maintained at 22 to 24°C and 76 to 86% relative humidity in a greenhouse with 10 h of daylight on average. Two weeks after inoculation with FL-Q11-1 or FL-Q12-1, all of the genotypes had developed TAN lesions with abundant sporulation, indicating susceptibility. On leaves inoculated with FL-Q09-1, however, no visible reaction was observed on PI 200492, and PI 567102B developed reddish-brown (RB) lesions associated with incomplete resistance. Although the lesions on Rpp1 and Rpp6 greenhouse seedlings inoculated with the FL-Q11-1 and FL-Q12-1 isolates were slightly darker than those that developed on Williams 82 plants or on detached leaflets, the profuse sporulation that is characteristic of the TAN infection type was observed. The higher virulence of the 2011 and 2012 Florida isolates on two soybean genotypes with Rpp1 and one with Rpp6 confirmed the presence of a P. pachyrhizi pathotype in north-central Florida that is more virulent against these genes than earlier populations from the southeastern United States. References: (1) S. Li. Crop Sci. 49:887, 2009. (2) Twizeyimana and Hartman. Plant Dis. 96:75, 2012. (3) Walker et al. Crop Sci. 51:678, 2011.

First Report of Sclerotinia Stem Rot Caused by Sclerotinia sclerotiorum on Brassica carinata in Florida.

Brassica carinata A. Braun, commonly referred to as Ethiopian rapeseed, a near relative of collards and mustard, has become the object of increasing interest as an oil crop. It has been reported that B. carinata adapts better and is more productive than B. napus (canola) in adverse conditions, such as clay and sandy soils and under low management cropping systems (1). In late February 2012, symptoms typical of sclerotinia stem rot were observed in B. carinata trials (cultivars 090867 EM and 080814 EM) at the University of Florida, North Florida Research and Education Center located in Quincy, FL. Approximately 20 to 30% of the B. carinata cultivar 090867 EM were observed to have symptoms and approximately 5% of cultivar 080814 EM displayed symptoms. Stems had white mycelia growing on the outside, plants were lodging and spherical to cylindrical, 3 to 8 mm, and black sclerotia were found outside and inside bleached stems. Sclerotia from diseased stems were surface sterilized and placed in 9-cm diameter petri plates on quarter strength potato dextrose agar (PDA) amended with 25% lactic acid. Fungal cultures consisting of white mycelia and medium-sized (mean 4 mm), black, irregular sclerotia were consistently recovered and identified as Sclerotinia sclerotiorum (Lib.) de Bary based on morphological characteristics (3). Sequence analyses were conducted on mycelium by extracting fungal DNA with the Qiagen DNeasy Plant Mini Kit (Valencia, CA). PCR amplification was performed using primers ITS1 and ITS4. The BLAST search revealed that the sequence (GenBank Accession No. JX307092) had 99 and 100% sequence identity with S. sclerotiorum GenBank accessions JN013184.1 and JN012606.1. Pathogenicity was determined by inoculating six 1-month-old B. carinata plants (cultivars 090867 EM and 080814 EM) that were grown in greenhouse pots (20 cm in diameter). Mycelia plugs (8 mm in diameter) were excised from the colony margin after 6 days of incubation at room temperature (approximately 25°C), and placed on stems, at the soil line, of B. carinata plants. Six control plants were inoculated with noncolonized PDA plugs. All plants were enclosed in plastic bags that had been sprayed with water on the inside to maintain high humidity and kept in the laboratory at room temperature (approximately 25°C). Symptoms similar to those observed in the field were evident after 3 days on inoculated plants and S. sclerotiorum was reisolated. In the controls, no symptoms developed and the fungus could not be isolated. The experiment was repeated with similar results. The majority of rapeseed production is in North Dakota, where sclerotinia stem rot caused by S. sclerotiorum is a major fungal disease affecting production (2). Currently, there is no significant B. carinata production in Florida; however, interest in biofuels could lead to an increase in planted acreage and sclerotinia stem rot could become a significant disease problem in areas of Florida were B. carinata is planted. To our knowledge, this is the first report of sclerotinia stem rot of B. carinata caused by S. sclerotiorum in Florida. References: (1) M. Cardone et al. Biomass and Bioenergy. 25:623, 2003. (2) L. E. del Río et al. Plant Dis. 91:191, 2007. (3) L. M. Kohn. Phytopathology 69:881, 1979.

First Report of Downy Mildew (Hyaloperonospora camelinae) on Camelina sativa in Florida.

Camelina sativa (L.) Crantz, Brassicaceae, whose common name is Crantz-large-seeded false flax, is an annual oilseed species. It is grown as a forage and biofuel crop in Europe and North America. False flax is an ideal low-input crop for biodiesel production, because of its low requirements for nitrogen fertilizer and pesticides. Production costs of this crop are substantially lower than those of many other oilseed crops such as rapeseed, corn, and soybean. It is an excellent rotation crop and can reduce disease and insect and weed pressure in wheat fields. During the spring of 2011, commercial and research plantings of C. sativa cultivar Calena in Liberty and Gadsden counties in north Florida developed symptoms typical of downy mildew. In spring of 2012, the same symptoms were observed in experimental plantings of false flax. A white downy mold was observed on the upper third portion of the plants, on the upper stem internodes, and on the developing seed. The affected stems exhibited a twisted growth. Conidiophores had main trunks with dichotomous branches terminating in slender curved tips. Conidia were ovoid and 28 to 45 (mean 36) µm long and 22 to 38 (mean 30) µm wide. Conidiophores were branched (three to four branches, each with six to eight curved tips) and ranged from 107 to 236 µm long and 5 to 14 µm wide. Mycelium was obtained directly from diseased plants for DNA extraction (Qiagen DNeasy Plant Mini Kit, Valencia, CA). Primers ITS1 and ITS4 were used for PCR amplification (4). The PCR product was sequenced bidirectionally with the PCR primers. A consensus nucleotide sequence (Accession JQ997103) was compared to those in the NCBI GenBank database using a BLAST search. The sequence was 99% similar to sequence from Hyaloperonospora camelinae (Gäum.) Göker, Voglmayr, Riethm, M. Weiss & Oberw. (Accession AY198249.1) with a 95% query coverage (1). Pathogenicity was established by applying white conidial masses of downy mildew from field samples to stems of 4-week-old plants grown in pots in a greenhouse maintained at 25 ± 2°C. Noninoculated plants maintained under the similar conditions served as control. Symptoms and signs of downy mildew developed after 14 days only on inoculated plants. Downy mildew constitutes a serious threat to the cultivation of C. sativa in Florida because of the humid climate favoring disease development. Diseased plants may reduce yield and disease management would increase production costs. H. camelinae was previously reported on C. sativa in Oregon, Minnesota, Montana (3), and Nebraska (2). To the best of our knowledge, this is the first report of downy mildew caused by H. camelinae on C. sativa in Florida. References: (1) M. Göker et al. Canad. J. Bot. 81:672, 2003. (2) R. M. Harveson et al. Plant Health Progress. 2011. doi: 10.1094/PHP-2011-1014-01-BR. (3) M. L. Putnam et al. Plant Health Progress. 2009. doi: 10.1094/PHP-2009-0910-01-BR. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990.

Effects of Silicon Applications on Soybean Rust Development Under Greenhouse and Field Conditions.

Soybean rust (SBR), caused by Phakopsora pachyrhizi, is one of the most destructive fungal diseases affecting soybean production. Silicon (Si) amendments were studied as an alternative strategy to control SBR because this element was reported to suppress a number of plant diseases in other host-pathogen systems. In greenhouse experiments, soybean cultivars inoculated with P. pachyrhizi received soil applications of wollastonite (CaSiO3) (Si at 0, 0.96, and 1.92 t ha-1) or foliar applications of potassium silicate (K2SiO3) (Si at 0, 500, 1,000, or 2,000 mg kg-1). Greenhouse experiment results demonstrated that Si treatments delayed disease onset by approximately 3 days. The area under disease progress curve (AUDPC) of plants receiving Si treatments also was significantly lower than the AUDPC of non-Si-treated plants. For field experiments, an average 3-day delay in disease onset was observed only for soil Si treatments. Reductions in AUDPC of up to 43 and 36% were also observed for soil and foliar Si treatments, respectively. Considering the natural delayed disease onset due to the inability of the pathogen to overwinter in the major soybean production areas of the United States, the delay in disease onset and the final reduction in AUDPC observed by the soil Si treatments used may lead to the development of SBR control practices that can benefit organic and conventional soybean production systems.

Urinary bisphenol A concentrations and ovarian response among women undergoing IVF.

Bisphenol A (BPA) is a synthetic chemical used in the manufacture of materials present in many common consumer products. In experimental animals, BPA caused oocyte aneuploidy and reduced production of oestradiol. In a prospective cohort study, we investigated the association between urinary BPA concentrations and ovarian response among women undergoing in vitro fertilization (IVF) at the Massachusetts General Hospital (MGH) Fertility Center. The geometric mean of two specific-gravity (SG) adjusted urinary BPA concentrations collected during each IVF cycle was used as the cycle-specific BPA exposure level. BPA concentrations were measured using online solid phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. Peak serum oestradiol was measured using the Elecsys Estradiol II immunoassay kit. Multivariable mixed effect models and Poisson regression models adjusting for correlation between multiple IVF cycles in the same woman were used to evaluate the association between urinary BPA concentrations and ovarian response, adjusting for age, BMI and day 3 follicle stimulating hormone (FSH) levels, a clinical measure of ovarian reserve. Urinary BPA concentrations were measured in 84 women (mean age 35.6 years) undergoing 112 IVF cycles; 23 women (27%) contributed more than one IVF cycle. BPA concentrations ranged from <0.4 to 25.5 microg/L (geometric mean 2.52 +/- SD 3.2); 15% of urine samples had concentrations <0.4 microg/L. Peak serum oestradiol levels correlated with the total number of oocytes retrieved per cycle (r = 0.65, p < 0.001). For each log unit increase in SG-BPA, there was an average decrease of 12% (95% CI: 4, 23%; p = 0.007) in the number of oocytes retrieved and an average decrease of 213 pg/ml (95% CI: -407, -20; p = 0.03) in peak oestradiol. BPA was detected in the urine of the majority of women undergoing IVF, and was inversely associated with number of oocytes retrieved and peak oestradiol levels.

Fusarium verticillioides (Saccardo) Nirenberg associated with hardlock of cotton.

Boll rots of cotton (Gossypium hirsutum L.) are common in the humid areas of the Southeastern US. One type of boll damage that may be differentiated from others is hardlock, with symptoms that include compression of the fibers within individual locules of mature, open cotton bolls without further obvious disintegration of the lint or damage to the carpel wall. The principal economic effect is that the boll's lint is unharvestable by mechanical cotton pickers. This disease is endemic to the Southeast and can cause severe yield losses up to 70% in some fields. Scanning electron microscopy images of fibers from hardlocked bolls showed flattened and twisted tissue compared to fibers from healthy bolls. Fusarium verticillioides (Saccardo) Nirenberg was the fungus most commonly isolated from seeds of developing cotton bolls. Flowers inoculated with F. verticillioides on the day of bloom by spraying a spore suspension onto the flowers developed significantly (P < 0.05) more hardlock symptoms compared to untreated controls. The infection process was analyzed using a F. verticillioides isolate tagged with green fluorescent protein (GFP). When it was applied to cotton flowers on the day of bloom, the GFP-tagged F. verticillioides strain was detected in the stigma and style by 2 days after bloom (DAB) and in developing seeds at 4, 6, 8, 10, 16, 20, 40, and 60 (open bolls) DAB. By 8 DAB, the GFP F. verticillioides was isolated from over 80% of developing seeds.

Removal of Wet Deposited Phakopsora pachyrhizi Urediniospores from Soybean Leaves by Subsequent Rainfall.

Urediniospores of Phakopsora pachyrhizi, the soybean rust fungus, have a high probability of being removed from a soybean leaf by water runoff associated with subsequent rainfall after wet deposition. The effects of rainfall intensity, subsequent spore-free rainfall duration, and soybean leaf sample height on uredinia density were used to evaluate the retention of urediniospores on soybean leaf tissue. Rainfall simulations of 45 and 85 mm/h were conducted on potted soybean plants that were inoculated with 2 min of urediniospore-injected simulated rainfall and exposed to 0, 1, and 30 min of subsequent spore-free rainfall. Urediniospore retention was estimated using uredinia density values obtained from a detached leaf bioassay for the sample heights of soil level, mid-canopy, and upper-canopy. Soil level leaflets inoculated with the 45 mm/h rainfall intensity treatment had a higher (P < 0.01) mean number of uredinia/cm2 than the 85 mm/h treatment, even though they were inoculated with approximately 40% fewer urediniospores. Subsequent spore-free rainfall reduced (P < 0.01) uredinia density by as much as 38 and 91% for the 1- and 30-min durations, respectively. The relationship between uredinia density proportion and depth of rainfall was best fit using an inverse power empirical model. Our results indicate that a majority of the wet deposited P. pachyrhizi urediniospores would be removed from soybean leaf surfaces by subsequent rainfall, but sufficient percentages of spores (10 to 25%) will likely remain on the leaf tissue long enough to germinate and infect during heavy summer rains lasting ≥30 min.

Effect of Fungicide and Timing of Application on Soybean Rust Severity and Yield.

Soybean rust, caused by Phakopsora pachyrhizi, is a devastating foliar disease of soybean that may cause significant yield losses if not managed by well-timed fungicide applications. To determine the effect of fungicide timing on soybean rust severity and soybean yield, field trials were completed in Paraguay (four locations), the United States (two locations), and Zimbabwe (one location) from 2005 to 2006. Treatments at each location included applications of tebuconazole, pyraclostrobin, or a combination of azoxystrobin + propiconazole, and in some locations pyraclostrobin + tebuconazole at the following soybean growth stages (GS): (i) GS R1 (beginning flowering), (ii) GS R3 (beginning pod), (iii) GS R5 (beginning seed), (iv) GS R1 + R3, (v) GS R3 + R5, and (vi) GS R1 + R3 + R5. Soybean yields from plots treated with fungicides were 16 to 114% greater than yields from no fungicide control plots in four locations in Paraguay, 12 to 55% greater in two locations in the United States, and 31% greater in Zimbabwe. In all locations, rust severity measured over time as area under the disease progress curve (AUDPC) was negatively correlated (r = -0.3, P < 0.0001) to yield. The effectiveness of any given treatment (timing of application and product applied) was often dependent on when rust was first detected and the intensity of its development. For example, when soybean rust was first observed before GS R3 (two locations in Paraguay), the plants in plots treated with a fungicide at GS R1 had the lowest AUPDC values and highest yields. When soybean rust was first observed after GS R3, plants treated with a fungicide at GS R3 and/or GS R5 had the lowest AUDPC values and highest yields with a few exceptions.

Structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function.

We have employed a structure-based three-dimensional quantitative structure-activity relationship (3D-QSAR) approach to predict the biochemical activity for inhibitors of T. cruzi dihydrofolate reductase-thymidylate synthase (DHFR-TS). Crystal structures of complexes of the enzyme with eight different inhibitors of the DHFR activity together with the structure in the substrate-free state (DHFR domain) were used to validate and refine docking poses of ligands that constitute likely active conformations. Structural information from these complexes formed the basis for the structure-based alignment used as input for the QSAR study. Contrary to indirect ligand-based approaches the strategy described here employs a direct receptor-based approach. The goal is to generate a library of selective lead inhibitors for further development as antiparasitic agents. 3D-QSAR models were obtained for T. cruzi DHFR-TS (30 inhibitors in learning set) and human DHFR (36 inhibitors in learning set) that show a very good agreement between experimental and predicted enzyme inhibition data. For crossvalidation of the QSAR model(s), we have used the 10% leave-one-out method. The derived 3D-QSAR models were tested against a few selected compounds (a small test set of six inhibitors for each enzyme) with known activity, which were not part of the learning set, and the quality of prediction of the initial 3D-QSAR models demonstrated that such studies are feasible. Further refinement of the models through integration of additional activity data and optimization of reliable docking poses is expected to lead to an improved predictive ability.

First Report of Soybean Rust Caused by Phakopsora pachyrhizi on Erythrina herbacea (Coral Bean).

Soybean rust (SBR), caused by the obligate fungus Phakopsora pachyrhizi Syd. & P. Syd., was initially reported on soybean (Glycine max L.) in Louisiana in 2004 and has since been reported on soybean and/or kudzu (Pueraria lobata (Willd.) Ohwi) in 9 states in 2005, 15 states in 2006, and 19 states in 2007 (1). The host range of P. pachyrhizi includes plants that are all in the Fabaceae or legume family. Six plant species in the United States have been reported as hosts of P. pachyrhizi: soybean, kudzu, Florida beggarweed (Desmodium tortuosum (Sw) DC.), dry bean (Phaseolus vulgaris L.), lima bean (P. lunatus L.), and scarlet runner bean (P. coccineus L.) (4). On 17 April 2008, a rust disease was observed on a weedy legume host with red showy flowers that was growing with kudzu in an overgrown vacant lot in the understory of live oak trees (Quercus virginiana Mill.) in Citra, FL. The discovery was made during routine scouting of this Integrated Pest Management Pest Information Platform for Extension and Education (IPM PIPE) mobile sentinel plot (3). The plant was confirmed by University of Florida botanists to be Erythrina herbaceae L., commonly known as coral bean. Coral bean is native to the southeastern United States and also is planted as a perennial ornamental. A sample of leaves exhibiting rust pustules characteristic of P. pachyrhizi uredinia was collected and examined with a microscope. Brown-to-brick red, angular lesions that were 3 to 11 mm in diameter (average 6.75 mm) were observed on the undersides of the leaves of two trifoliates. Within these lesions, there were several uredinia, some exuding hyaline, echinulate urediniospores (20 × 25 µm). The visual diagnosis and the species of the rust fungus were confirmed to be P. pachyrizi by a real-time PCR protocol (2). The diagnosis on this new host was verified by a USDA, APHIS National Mycologist in Beltsville, MD. Coral bean may serve as an additional overwintering host for P. pachyrhizi in the southeast. To our knowledge, this is the first report of soybean rust caused by P. pachyrhizi on E. herbaceae. References: (1) R. S. C. Christiano and H. Scherm, Phytopathology 97:1428, 2007. (2) R. D. Frederick et al. Phytopathology 92:217, 2002. (3) S. A. Isard et al. Online publication. doi:10.1094/PHP-2006-0915-01-RV. Plant Health Progress, 2006. (4) T. L. Slaminko et al. Plant Dis. 92:767, 2008.

Improving novel motor learning through prior high contextual interference training.

The primary objective of the present experiment was to examine the influence of recent practice in a random and blocked format for future motor learning. First, individuals practiced three unique discrete sequence production tasks in either a blocked or random schedule. One day later, all individuals practiced a new motor sequence not previously practiced. On day three, mean total time for the test performance of the original three motor sequences was lower for individuals that practiced in a random format. This emerged as a significant reduction in mean total time from the completion of practice and the test trials implicating offline consolidation as a key contributor to the random practice performance advantage. A novel finding from the present work was that the acquisition of the novel discrete sequence production task practiced on Day 2 was better for individuals that had prior random rather than blocked practice experience. This benefit was robust appearing early during acquisition as significantly lower mean total time. This benefit from random practice experience remained during the delayed test trials administered on Day 3 for the novel motor sequence.

Learning and transfer of a relative phase pattern and a joint amplitude ratio in a rhythmic multijoint arm movement.

According to the coordination dynamics perspective, one can characterize the learning of novel relative phase patterns as the formation of a stable attractor in the coordination landscape of the order parameter relative phase. The authors examined 18 participants' learning and transfer of a 90 degrees relative phase pattern and a 0.6-joint-amplitude ratio between the elbow and wrist. Variability in the relative phasing and the joint amplitude ratio between the elbow and wrist decreased with practice. Positive transfer of the 90 degrees relative phase pattern was not dependent on the learning arm (dominant or nondominant). Positive transfer of the joint amplitude ratio was dependent on the learning arm and the direction of transfer. The results demonstrated that relative phase is an order parameter that characterizes the coordination dynamics of learning and transferring multijoint arm movements, and they provide preliminary evidence that joint amplitude ratios act as order parameters in the learning and transfer of multijoint arm movements.

Influence of Flower Thrips on Fusarium Hardlock Severity.

Cotton (Gossypium hirsutum) fiber is sometimes affected by hardlock, which is characterized by a failure of the fiber to expand outward from the boll at maturity. Because affected fiber is inaccessible to mechanical harvesters, yield loss can be considerable. Hardlock has been linked to infection by Fusarium verticillioides. The involvement of flower thrips (Frankliniella spp.), which are commonly found in cotton flowers, was explored. At 1100 h, approximately 10% of cotton flowers contained thrips that were carrying F. verticillioides. The effect of thrips and/or Fusarium in flowers and bolls was explored under greenhouse conditions. Exposing flowers to Fusarium and thrips resulted in bolls with the most severe symptoms. Exposure to either Fusarium or thrips alone resulted in more hardlock than was noted in the control group. The impact of thrips was also evaluated under field conditions. Field plots were treated with insecticides, a fungicide, both, or left untreated. Insecticides reduced thrips numbers and reduced hardlock severity. The fungicide had no impact on thrips numbers and was less effective at reducing hardlock. Combining insecticide and fungicide applications was no more effective than using insecticides alone, although it more frequently increased yield. The untreated control plots generally had the most severe hardlock and lowest yields. Reducing hardlock severity resulted in higher yields, although not consistently. These studies suggest that thrips increase the severity of hardlock, and reducing their numbers may diminish hardlock severity.

Male caffeine and alcohol intake in relation to semen parameters and in vitro fertilization outcomes among fertility patients.

Much of the literature on the impact of male caffeine and alcohol intake on reproductive outcomes has utilized semen quality as a proxy for male fertility, although semen parameters have a limited predictive value for spontaneous pregnancy. The objective of this study was to investigate whether male caffeine and alcohol intakes are associated with semen parameters and assisted reproductive technology outcome. The Environment and Reproductive Health Study, an ongoing prospective cohort study, enrolls subfertile couples presenting for treatment at an academic fertility center (2007-2012). A total of 171 men with 338 semen analyses and 205 assisted reproductive technology cycles were included in this analysis. Diet was assessed using a 131-item food frequency questionnaire. Mixed models adjusting for potential confounders were used to evaluate the relationships of male caffeine and alcohol intakes with semen parameters and assisted reproductive technology outcomes. There was no association between male caffeine and alcohol intake and semen quality. Male caffeine intake was negatively related to live birth after assisted reproductive technologies (p-trend < 0.01), and male alcohol intake was positively related to live birth after assisted reproductive technologies (p-trend = 0.04). Adjusted live birth rate among couples with a male partner in the highest quartile of caffeine intake (≥272 mg/day) compared to couples with a male partner in the lowest quartile of intake (<99 mg/day) was 19% vs. 55%, respectively, p < 0.01. In terms of alcohol intake, adjusted live birth rate among couples with a male partner in the highest quartile of alcohol intake (≥22 g/day) compared to couples with a male partner in the lowest quartile of intake (<3 g/day) was 61% vs. 28%, respectively, p = 0.05. In conclusion, male pre-treatment caffeine and alcohol intakes were associated with live birth after assisted reproductive technologies, but not with semen parameters, among fertility patients.

First Report of Soybean Rust Caused by Phakopsora pachyrhizi on Phaseolus spp. in the United States.

Phakopsora pachyrhizi Syd. & P. Syd., the cause of soybean rust, was first observed in the continental United States in November 2004 (2). During the growing season of 2005, P. pachyrhizi was confirmed on soybean (Glycine max) and/or kudzu (Pueraria montana) in nine states in the southern United States. It is known that P. pachyrhizi has a much larger host range within the Fabaceae family. On 29 September 2005 in Quincy, FL, 45 entries of mostly large-seeded legumes were planted next to soybeans that were infected with P. pachyrhizi. Several seeds of each entry were planted on one hill. Soybean plants growing adjacent to these potential hosts had 15 to 25% of the leaf area affected, 95% incidence, and 73% defoliation on 16 November. On 7 December 2005, all the plants of Phaseolus coccineus L. (scarlet runner bean, PI311827), Phaseolus lunatus L. (lima bean, PI583558), and two Phaseolus vulgaris L. (kidney bean) cvs. Red Hawk and California Early Light Red Kidney (CELRK) were found to have leaves with suspected rust lesions. These plants were at physiological maturity but had not senesced. None of the hosts had been inoculated other than from spores produced by the adjacent rust-infected soybean plants or from unknown locations. On the basis of microscopic examination, suspected infected leaves from plants of the Phaseolus spp. had rust pustules characteristic of P. pachyrhizi uredinia. Uredinia were counted within a randomly selected 2-cm2 area of one leaf of each sample. The mean and range of uredinia per lesion for Phaseolus coccineus was 29 uredinia with a range of 0 to 3 uredinia per lesion, Phaseolus lunatus had 2 uredinia with 0 to 1 uredinium per lesion, Phaseolus vulgaris cv. Red Hawk had 22 uredinia with 0 to 5 uredinia per lesion, and Phaseolus vulgaris cv. CELRK had 43 uredinia with 0 to 4 uredinia per lesion. Polymerase chain reactions using two sets of primers (Ppa1/Ppa2 and Pme1/Pme2) were performed on DNA extracted from leaves of the three species with sporulating rust pustules (1). The results of these tests and further tests conducted by the USDA/APHIS confirmed that P. pachyrhizi was the causal organism for the observed rust. References: (1) P. F. Harmon et al. On-line publication. doi:10.1094/PHP-2005-0613-01-RS. Plant Health Progress, 2005. (2) R. W. Schneider et al. Plant Dis. 89:774, 2005.

New bicyclic antidepressant agent. Synthesis and activity of napactadine and related compounds.

A number of N,N'-dialkylarylamidines were synthesized and evaluated for antidepressant activity. Several of these compounds were synthesized from the corresponding nitriles by a new method. Slight structural modification in the series caused a marked change in biological activity and led to compounds as active as imipramine. The arylacetamidine, N,N'-dimethyl-2-naphthaleneethanimidamide hydrochloride (33) (napactadine) was selected for clinical study. Forty-eight additional analogues of 33, including a number of N-alkylamidines, were prepared.