The isolation, structure determination and cytotoxicity of the new fungal metabolite, trichodermamide C

Chemical investigations of a culture broth from the endophytic fungus Eupenicillium sp. afforded the new modified dipeptide trichodermamide C 1. The structure of 1 was established following the analysis of NMR, UV, IR, MS and X-ray diffraction data. Trichodermamide C was shown by high content screening to display cytotoxicity towards the human colorectal carcinoma HCT116 and human lung carcinoma A549 with IC₅₀ values of 0.68 and 4.28 μg/ml, respectively.     

Novel phenotypes identified by plasma biochemical screening in the mouse

We used ENU mutagenesis in the mouse for the rapid generation of novel mutant phenotypes for both gene function studies and use as new animal models of human disease (Nolan et al. 2000b). One focus of the program was the development of a blood biochemistry screen. At 8-12 weeks of age, approximately 300 ml of blood was collected from F1 offspring of ENU mutagenized male mice. This yielded approximately 125 ml of plasma, used to perform a profile of 17 standard biochemical tests on an Olympus analyzer. Cohorts of F1 mice were also aged and then retested to detect late onset phenotypes. In total, 1,961 F1s were screened. Outliers were identified by running means and standard deviations. Of 70 mice showing consistent abnormalities in plasma biochemistry, 29 were entered into inheritance testing. Of these, 9 phenotypes were confirmed as inherited, 10 found not to be inherited, and 10 are still being tested. Inherited mutant phenotypes include abnormal lipid profiles (low total and HDL cholesterol, high triglycerides); abnormalities in bone and liver metabolism (low ALP, high ALP, high ALT, and AST); abnormal plasma electrolyte levels (high sodium and chloride); as well as phenotypes of interest for the study of diabetes (high glucose). The gene loci bearing the mutations are currently being mapped and further characterized. Our results have validated our biochemical screen, which is applicable to other mutagenesis projects, and we have produced a new set of mutants with defined metabolic phenotypes.     

Reliably Detecting Clinically Important Variants Requires Both Combined Variant Calls and Optimized Filtering Strategies

A diversity of tools is available for identification of variants from genome sequence data. Given the current complexity of incorporating external software into a genome analysis infrastructure, a tendency exists to rely on the results from a single tool alone. The quality of the output variant calls is highly variable however, depending on factors such as sequence library quality as well as the choice of short-read aligner, variant caller, and variant caller filtering strategy. Here we present a two-part study first using the high quality ‘genome in a bottle’ reference set to demonstrate the significant impact the choice of aligner, variant caller, and variant caller filtering strategy has on overall variant call quality and further how certain variant callers outperform others with increased sample contamination, an important consideration when analyzing sequenced cancer samples. This analysis confirms previous work showing that combining variant calls of multiple tools results in the best quality resultant variant set, for either specificity or sensitivity, depending on whether the intersection or union, of all variant calls is used respectively. Second, we analyze a melanoma cell line derived from a control lymphocyte sample to determine whether software choices affect the detection of clinically important melanoma risk-factor variants finding that only one of the three such variants is unanimously detected under all conditions. Finally, we describe a cogent strategy for implementing a clinical variant detection pipeline; a strategy that requires careful software selection, variant caller filtering optimizing, and combined variant calls in order to effectively minimize false negative variants. While implementing such features represents an increase in complexity and computation the results offer indisputable improvements in data quality.     

Type 2 Diabetes with Comorbid Depression in Relation to Cognitive Impairment: an Opportunity for Prevention?

Studies show poor glycemic control is associated with increased risk of dementia among patients with Type 2 diabetes, indicating potential for prevention of dementia with improved glycemia. Emerging evidence suggests that a relationship between short-term glycemic control and cognitive function exists in Type 2 diabetes. However, detailed mechanisms relating diabetic dementia are lacking, as other concurrent conditions, such as depression, may also increase the risk of dementia in Type 2 diabetes. We examined the effects of glycemic control and depression on cognitive function in 88 patients (mean age, 67 ± 4 years) whose A1c (glycosylated hemoglobin) levels, comorbid depression, mini-mental state examination (MMSE) scores were recorded at baseline. Seventeen patients had depression; 14 agreed on anti-depressants. In 6 months, 69 patients reached A1c goal of < 7% (A1c from 9.7 ± 0.8 to 6.4 ± 0.3) while cognition improved significantly (MMSE scored from 20.2 ± 3.5 to 26.2 ± 2.1, p < 0.05). Cognitive increment in controlled diabetes was more consistently observed if their underlying depression was effectively treated (n ? 14). Nineteen patients did not reach A1c goal of < 7% (A1c from 9.6 ± 0.9 to 8.9 ± 0.9) while cognitive increment was minimal (MMSE scored from 20.6 ± 4.9 to 21.3 ± 5.1, p > 0.05). Cognitive decrements were observed among depressed diabetics who refused anti-depressants. Multivariate analysis adjusted for age, education, alcohol use, and other variables yielded similar results. We found controlled glycemia and depression prevent cognitive decline. Further research into mechanisms of cognitive impairment in diabetes may allow us to challenge the concept of dementia in those patients as an irremediable disease.     

The potential impacts of the arrival of the harlequin ladybird, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), in Britain

Abstract.  1. The harlequin ladybird, Harmonia axyridis , has recently arrived in Britain.
2. This species has been introduced from Asia into many parts of the world for biological control purposes.
3. In many parts of North America it has become the predominant aphidophagous coccinellid in less than 20 years, and in north-western Europe it is spreading and increasing in number rapidly.
4. Since establishment in North America and continental Europe, reports of its effectiveness as a biological control agent of aphids and coccids have been accompanied by accounts of negative effects on other aphidophagous species and humans.
5. Here the potential impacts of the arrival of the harlequin ladybird in Britain are assessed.     

Comparison of the symptoms of exercise-induced muscle damage after an initial and repeated bout of plyometric exercise in men and boys.

The purpose of this study was to compare symptoms of exercise-induced muscle damage after an initial and repeated bout of plyometric exercise in men and boys. Ten boys (9-10 yr) and 10 men (20-29 yr) completed two bouts of eight sets of 10 plyometric jumps, 2 wk apart. Perceived soreness (0-10, visual analog scale), isometric strength of the quadriceps at six knee flexion angles, and countermovement jump and squat jump height were assessed before and at 30 min, 24 h, 48 h, and 72 h after each bout. All variables followed the expected patterns of change in men, with soreness peaking at 24-48 h (5.8 +/- 1.7) and decrements in muscle function peaking at 30 min after the first bout (73-85% of baseline scores). Symptoms remained for 72 h after the first bout in men. In boys, symptoms were much less severe and peaked at 30 min (visual analog scale = 2.1 +/- 1.8, functional decrements 87-92% of baseline) and, with the exception of soreness, returned to baseline after 24 h. After the second bout of plyometric exercise, the level of soreness and decrements in countermovement jump, squat jump, and isometric strength were lower, although the effect was stronger in men, in all cases. The results of this study suggest that although children may experience symptoms of muscle damage after intensive plyometric exercise, they are much less severe. A prior bout of plyometric exercise also appears to provide children with some protection from soreness after a subsequent bout of plyometric exercise. Explanations for milder symptoms of exercise-induced muscle damage in children include greater flexibility leading to less overextension of sarcomeres during eccentric exercise, fewer fast-twitch muscle fibers, and greater and perhaps more varied habitual physical activity patterns.     

Evaluation of dyes for marking painted apple moths (Teia anartoides Walker, Lep. Lymantriidae) used in a sterile insect release program

Abstract  Two methods of marking painted apple moth ( Teia anartoides Walker, Lepidoptera: Lymantriidae), internal and external dyes, were investigated for use with the sterile insect technique, to ensure that wild and released moths could be distinguished absolutely during the eradication program. Calco Red dye was used to mark all moths internally. It was added to artificial diet and was detectable in the adults. Dye was incorporated into the larval diet at four rates. No differences were observed in mortality of the larvae, fertility of the adult female or response of male moths to virgin females in a flight tunnel. Fluorescent powder dyes were used throughout the sterile insect program to identify irradiated moths, as well as their release location and colony. However, the powdered dyes reduced the ability of male moths to detect a component of the sex pheromone in electro-antennogram tests and to respond to a calling virgin female in flight tunnel trials. Field trials suggest that moths may subsequently overcome these negative effects and respond to female moths, as moths heavily coated in dye were recaptured.     

Electromyography and the evolution of motor control: limitations and insights

Electromyography (EMG), or the study of muscle activation patterns,has long been used to infer central nervous system (CNS) controlof the musculoskeletal system and the evolution of that control.As the activation of the muscles at the level of the peripheryis a reflection of the interaction of descending influencesand local reflex control, EMG is an important tool in integratedinvestigations of the evolution of coordination in complex,musculoskeletal systems. Yet, the use of EMG as a tool to understandthe evolution of motor control has its limitations. We herereview the potential limitations and opportunities of the useof EMG in studying the evolution of motor control in vertebratesand provide original previously unpublished data to illustratethis. The relative timing of activation of a set of musclescan be used to evaluate CNS coordination of the components ina musculoskeletal system. Studies of relative timing revealtask-dependent variability in the recruitment of different populationsof muscle fibers (i.e., different fiber types) within a singlemuscle, and left–right asymmetries in activation thatneed to be taken into account in comparative studies. The magnitudeof muscle recruitment is strongly influenced by the instantaneousdemands imposed on the system, and is likely determined by localreflex-control systems. Consequently, using EMG to make meaningfulinferences about evolutionary changes in musculoskeletal controlrequires comparisons across similar functional tasks. Moreover,our data show that inferences about the evolution of motor controlare limited in their explanatory power without proper insightsinto the kinematics and dynamics of a system.