Non-targeted analysis of spatial metabolite composition in strawberry (Fragariaxananassa) flowers

Formation of flower organs and the subsequent pollination process require a coordinated spatial and temporal regulation of particular metabolic pathways. In this study a comparison has been made between the metabolite composition of individual flower organs of strawberry (Fragaria × ananassa) including the petal, sepal, stamen, pistil and the receptacle that gives rise to the strawberry fruit. Non-targeted metabolomics analysis of the semi-polar secondary metabolites by the use of UPLC-qTOF-MS was utilized in order to localize metabolites belonging to various chemical classes (e.g. ellagitannins, proanthocyanidins, flavonols, terpenoids, and spermidine derivatives) to the different flower organs. The vast majority of the tentatively identified metabolites were ellagitannins that accumulated in all five parts of the flower. Several metabolite classes were detected predominantly in certain flower organs, as for example spermidine derivatives were present uniquely in the stamen and pistil, and the proanthocyanidins were almost exclusively detected in the receptacle and sepals. The latter organ was also rich in terpenoids (i.e. triterpenoid and sesquiterpenoid derivatives) whereas phenolic acids and flavonols were the predominant classes of compounds detected in the petals. Furthermore, we observed extensive variation in the accumulation of metabolites from the same class in a single organ, particularly in the case of ellagitannins, and the flavonols quercetin, kaempferol and isorhamnetin. These results allude to spatially-restricted production of secondary metabolite classes and specialized derivatives in flowers that take part in implementing the unique program of individual organs in the floral life cycle.     

The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease

Vascular diseases such as atherosclerosis, stroke or myocardial infarction are a significant public health problem worldwide. Attempts to prevent vascular diseases often imply modifications and improvement of causative risk factors such as high blood pressure, obesity, an unfavorable profile of blood lipids or insulin resistance. In addition to numerous preventive and therapeutic drug regimens, there has been increased focus on identifying dietary compounds that may contribute to cardiovascular health in recent years. Food-derived bioactive peptides represent one such source of health-enhancing components. They can be released during gastrointestinal digestion or food processing from a multitude of plant and animal proteins, especially milk, soy or fish proteins. Biologically active peptides are considered to promote diverse activities, including opiate-like, mineral binding, immunomodulatory, antimicrobial, antioxidant, antithrombotic, hypocholesterolemic and antihypertensive actions. By modulating and improving physiological functions, bioactive peptides may provide new therapeutic applications for the prevention or treatment of chronic diseases. As components of functional foods or nutraceuticals with certain health claims, bioactive peptides are of commercial interest as well. The current review centers on bioactive peptides with properties relevant to cardiovascular health.     

Synthesis of potent pyrrolidine influenza neuraminidase inhibitors

The synthesis of several pyrrolidine inhibitor analogs is described that possess nanomolar in vitro potencies against the neuraminidase enzymes expressed by the B/Memphis/3/89 and A/N1/PR/8/34 influenza strains.     

Effect of 6-month athletic training on motor abilities in seven-year-old schoolgirls

The effects of six-month athletic training on improving motor abilities in 7-year-old schoolgirls were assessed. Analysis of the results of 12 motor tests showed significant improvement in the study group (n = 38) in comparison with control group (n = 140) subjected to conventional physical education classes only. The improvement referred to the variables of aerobic endurance (3-min run), flexibility (forward bow), explosive strength (ball throwing and 20-m run), keeping balance (bench standing), static strength (bent arm hang), and repetitive strength (sit-ups). These are probably adaptive changes brought up by discriminant functions. The varimax factor and discriminative function correlations indicated that all four factors of changes contributed significantly to the explanation of discriminative function. An almost equally high correlation of varimax factors and discriminative function was obtained on the basis of differences in the third factor responsible for changes in the frequency of movements and in the explosive strength of the jump type; in the second factor responsible for changes in coordination with changes in the repetitive strength of the body; and in the fourth factor responsible for changes in the explosive strength of the throw and sprint types with changes and endurance.     

Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS.     

High potency improvements to weak aryl uracil HCV polymerase inhibitor leads

Described herein is the development of a potent non-nucleoside, small molecule inhibitor of genotype 1 HCV NS5B Polymerase. A 23 μM inhibitor that was active against HCV polymerase was further elaborated into a potent single-digit nanomolar inhibitor of HCV NS5B polymerase by additional manipulation of the R and R₁ substituents. Subsequent modifications to improve physical properties were made in an attempt to achieve an acceptable pharmacokinetic profile.     

Differential Roles of Fibroblast Growth Factor Receptors (FGFR) 1, 2 and 3 in the Regulation of S115 Breast Cancer Cell Growth

Fibroblast growth factors (FGFs) regulate the growth and progression of breast cancer. FGF signaling is transduced through FGF receptors 1–4, which have oncogenic or anti-oncogenic roles depending on the ligand and the cellular context. Our aim was to clarify the roles of FGFR1–3 in breast cancer cell growth in vitro and in vivo. Pools of S115 mouse breast cancer cells expressing shRNA against FGFR1, 2 and 3 were created by lentiviral gene transfer, resulting in cells with downregulated expression of FGFR1, FGFR2 or FGFR3 (shR1, shR2 and shR3 cells, respectively) and shLacZ controls. FGFR1-silenced shR1 cells formed small, poorly vascularized tumors in nude mice. Silencing of FGFR2 in shR2 cells was associated with strong upregulation of FGFR1 expression and the formation of large, highly vascularized tumors compared to the control tumors. Silencing FGFR3 did not affect cell survival or tumor growth. Overexpressing FGFR2 in control cells did not affect FGFR1 expression, suggesting that high FGFR1 expression in shR2 cells and tumors was associated with FGFR2 silencing by indirect mechanisms. The expression of FGFR1 was, however, increased by the addition of FGF-8 to starved shLacZ or MCF-7 cells and decreased by the FGFR inhibitor PD173074 in shR2 cells with an elevated FGFR1 level. In conclusion, our results demonstrate that FGFR1 is crucial for S115 breast cancer cell proliferation and tumor growth and angiogenesis, whereas FGFR2 and FGFR3 are less critical for the growth of these cells. The results also suggest that the expression of FGFR1 itself is regulated by FGF-8 and FGF signaling, which may be of importance in breast tumors expressing FGFs at a high level.