Choleretic effects of yarrow (Achillea millefolium s.l.) in the isolated perfused rat liver

Different species from the Achillea millefolium aggregate are used against gastrointestinal and hepato-biliary disorders in traditional European medicine. In this work, a fraction enriched in dicaffeoylquinic acids (DCCAs) and luteolin-7-O-β-d-glucuronide was investigated on its choleretic effect in the isolated perfused rat liver (IPRL) compared to cynarin (1,3-DCCA), the main choleretic compound of Cynara scolymus L. A fraction containing 3,4-, 3,5- and 4,5-DCCA and luteolin-7-O-β-d-glucuronide was prepared by solid phase extraction from a 20% methanolic extract of yarrow. A total amount of 48.8% DCCAs and 3.4% luteolin-7-O-β-d-glucuronide was determined by HPLC analysis with cynarin as internal standard. IPRL experiments revealed a dose-dependant increase in bile flow (23–44–47%) by the Achillea fraction. Choleresis was two- to three-fold higher than that of cynarin. The combined effect of DCCAs and luteolin-7-O-β-d-glucuronide stimulated bile flow more effectively than the single compound cynarin. Due to their polar structure, these compounds are quantitatively extracted into teas and tinctures; hence, they seem to be the choleretic active principles in the traditional application forms of yarrow.     

A note on approximating the cumulative distribution function of the time to tumor onset in multistage models

The general multistage theory of carcinogenesis is a very special type of interconnected birth and death process in which the final state is absorbing and all states except the first one are empty at time zero. An approximation proposed by Whittemore and Keller (1978, SIAM Review 20, 1-30) is assessed. It is shown that the adequacy of this approximation depends on the number of malignant cells resulting from a single normal cell. If more than one malignant cell is likely to occur, the approximation will fail.     

Environment outweighs the effects of fishing in regulating demersal community structure in an exploited marine ecosystem

Global climate change has already caused bottom temperatures of coastal marine ecosystems to increase worldwide. These ecosystems face many pressures, of which fishing is one of the most important. While consequences of global warming on commercial species are studied extensively, the importance of the increase in bottom temperature and of variation in fishing effort is more rarely considered together in these exploited ecosystems. Using a 17 year time series from an international bottom trawl survey, we investigated covariations of an entire demersal ecosystem (101 taxa) with the environment in the Celtic Sea. Our results showed that over the past two decades, biotic communities in the Celtic Sea were likely controlled more by environmental variables than fisheries, probably due to its long history of exploitation. At the scale of the entire zone, relations between taxa and the environment remained stable over the years, but at a local scale, in the center of the Celtic Sea, dynamics were probably driven by interannual variation in temperature. Fishing was an important factor structuring species assemblages at the beginning of the time series (2000) but decreased in importance after 2009. This was most likely caused by a change in spatial distribution of fishing effort, following a change in targeted taxa from nephrops to deeper water anglerfish that did not covary with fishing effort. Increasing bottom temperatures could induce additional changes in the coming years, notably in the cold‐water commercial species cod, hake, nephrops, and American plaice. We showed that analyzing covariation is an effective way to screen a large number of taxa and highlight those that may be most susceptible to future simultaneous increases in temperature and changes in exploitation pattern by fisheries. This information can be particularly relevant for ecosystem assessments.     

Estimation of Unsteady Aerodynamics in the Wake of a Freely Flying European Starling (Sturnus vulgaris)

Wing flapping is one of the most widespread propulsion methods found in nature; however, the current understanding of the aerodynamics in bird wakes is incomplete. The role of the unsteady motion in the flow and its contribution to the aerodynamics is still an open question. In the current study, the wake of a freely flying European starling has been investigated using long-duration high-speed Particle Image Velocimetry (PIV) in the near wake. Kinematic analysis of the wings and body of the bird has been performed using additional high-speed cameras that recorded the bird movement simultaneously with the PIV measurements. The wake evolution of four complete wingbeats has been characterized through reconstruction of the time-resolved data, and the aerodynamics in the wake have been analyzed in terms of the streamwise forces acting on the bird. The profile drag from classical aerodynamics was found to be positive during most of the wingbeat cycle, yet kinematic images show that the bird does not decelerate. It is shown that unsteady aerodynamics are necessary to satisfy the drag/thrust balance by approximating the unsteady drag term. These findings may shed light on the flight efficiency of birds by providing a partial answer to how they minimize drag during flapping flight.     

IBC’s 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics International Conferences and the 2012 Annual Meeting of The Antibody Society

The 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences, and the 2012 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 3–6, 2012 in San Diego, CA. The meeting drew over 800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a prelude to the main events, a pre-conference workshop held on December 2, 2012 focused on intellectual property issues that impact antibody engineering. The Antibody Engineering Conference was composed of six sessions held December 3–5, 2012: (1) From Receptor Biology to Therapy; (2) Antibodies in a Complex Environment; (3) Antibody Targeted CNS Therapy: Beyond the Blood Brain Barrier; (4) Deep Sequencing in B Cell Biology and Antibody Libraries; (5) Systems Medicine in the Development of Antibody Therapies/Systematic Validation of Novel Antibody Targets; and (6) Antibody Activity and Animal Models. The Antibody Therapeutics conference comprised four sessions held December 4–5, 2012: (1) Clinical and Preclinical Updates of Antibody-Drug Conjugates; (2) Multifunctional Antibodies and Antibody Combinations: Clinical Focus; (3) Development Status of Immunomodulatory Therapeutic Antibodies; and (4) Modulating the Half-Life of Antibody Therapeutics. The Antibody Society’s special session on applications for recording and sharing data based on GIATE was held on December 5, 2012, and the conferences concluded with two combined sessions on December 5–6, 2012: (1) Development Status of Early Stage Therapeutic Antibodies; and (2) Immunomodulatory Antibodies for Cancer Therapy.     

New zeolite adsorbents for downstream processing of polyphenols from renewable resources

Commercial materials with polyvinylpolypyrrolidone and polymeric amberlites (XAD7HP, XAD16) are commonly used for the adsorptive downstream processing of polyphenols from renewable resources. In this study, beta‐zeolite‐based adsorbent systems were examined, and their properties were compared to organic resins. Batch adsorption experiments were conducted with synthetic solutions of major polyphenols. Adsorption isotherms and desorption characteristics of individual adsorbent were determined based on these results. Maximum adsorption capacities were calculated using the Langmuir model. For example, the zeolites had capacities up to 203.2 mg/g for ferulic acid. To extend these results to a complex system, additional experiments were performed on rapeseed meal and wheat seed extracts as representative renewable resources. HPLC analysis showed that with 7.5% w/v, which is regarded as the optimum amount of zeolites, zeolites A and B could bind 100% of the major polyphenols as well as release polyphenols at high yields. Additionally, regeneration experiments were performed with isopropyl alcohol at 99°C to evaluate how zeolites regenerate under mild conditions. The results showed only a negligible loss of adsorption capacity and no loss of desorption capacity. In summary, it was concluded that beta‐zeolites were promising adsorbents for developing new processes to isolate polyphenols from renewable resources.     

Determinants of Physiological and Perceived Physiological Stress Reactivity in Children and Adolescents

Aims

Abnormal physiological stress reactivity is increasingly investigated as a vulnerability marker for various physical and psychological health problems. However, studies are inconsistent in taking into account potential covariates that may influence the developing stress system. We systematically tested determinants (individual, developmental, environmental and substance use-related) of physiological and perceived physiological stress reactivity. We also examined the relation between physiological and perceived physiological stress reactivity.

Method

In a stratified sample of 363 children (7–12 years) and 344 adolescents (13–20 years) from the general population, we examined cortisol, heart rate, respiratory sinus arrhythmia and perceived physiological stress reactivity to a psychosocial stress procedure.

Results

Using multivariate linear regression models, we found that individual, developmental, environmental and substance use-related factors were related to each of the stress response indices. These determinant factors were different for each of the stress reactivity indices, and different in children versus adolescents. Perceived physiological stress reactivity predicted cortisol reactivity in adolescents only. All other relations between perceived physiological and physiological stress reactivity were not significant.

Conclusions

As physiological stress variables are often examined as vulnerability markers for the development of health problems, we maintain that it is essential that future studies take into consideration factors that may account for found relations. Our study provides an overview and indication of which variables should be considered in the investigation of the relation between physiological stress indices and illness.     

The Linker Pivot in Ci-VSP: The Key to Unlock Catalysis

In the voltage-sensitive phosphatase Ci-VSP, conformational changes in the transmembrane voltage sensor domain (VSD) are transduced to the intracellular catalytic domain (CD) leading to its dephosphorylation activity against membrane-embedded phosphoinositides. The linker between both domains is proposed to be crucial for the VSD-CD coupling. With a combined approach of electrophysiological measurements on Xenopus oocytes and molecular dynamics simulations of a Ci-VSP model embedded in a lipid bilayer, we analyzed how conformational changes in the linker mediate the interaction between the CD and the activated VSD. In this way, we identified specific residues in the linker that interact with well-defined amino acids in one of the three loops forming the active site of the protein, named TI loop. With our results, we shed light into the early steps of the coupling process between the VSD and the CD, which are based on fine-tuned electrostatic and hydrophobic interactions between the linker, the membrane and the CD.