Challenging the Biomedical Notion of ‘Active Substance’

Sowa Rigpa (Tibetan medicine) has been practiced across vast regions of Central and South Asia for centuries. In this medical tradition, it is common practice to dynamically adapt the mainly herbal formulas according to the regional flora and local conditions, and to use local variants of ingredients. Consequently, one Tibetan ingredient name within a specific formula can signify a variety of therapeutically fitting botanical items, which appear quite different from the perspective of modern taxonomy. This has led many researchers to understand the botanical plasticity of Tibetan medical formulas as misidentifications. We develop an alternative approach, exploring the advantages of this plasticity as a necessary practice to fulfill economic and therapeutic needs. This perspective piece questions the biomedical paradigm of single ‘active substances,’ since botanically unrelated plants with different chemical compositions can be similarly therapeutically effective. From a systems biology perspective, network pharmacology lets us understand the correspondence of illness and medicine as a semiotic process in which herbal formulations act via their ‘pleiotropic signatures’: complex webs of signal pathways that connect and act on multiple levels of organization in the body

Interference and interaction effects in multi-level quantum dots

Using renormalization group techniques, we study spectral and transport properties of a spinless interacting quantum dot consisting of two levels coupled to metallic reservoirs. For strong Coulomb repulsion $U$ and an applied Aharonov-Bohm phase $\phi$, we find a large direct tunnel splitting $|\Delta|\sim (\Gamma/\pi)|\cos(\phi/2)|\ln(U/\omega_c)$ between the levels of the order of the level broadening $\Gamma$. As a consequence we discover a many-body resonance in the spectral density that can be measured via the absorption power. Furthermore, for $\phi=\pi$, we show that the system can be tuned into an effective Anderson model with spin-dependent tunneling.Comment: 5 pages, 4 figures included, typos correcte

Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice

BACKGROUND/AIMS: Recent reports suggest that the adipose tissue and adipokines are potent modulators of inflammation. However, there is only scarce knowledge on the functional role and regulation of endogenous adiponectin in non-fat tissues such as the liver under conditions of acute inflammation. METHODS: In the present study, we investigated adiponectin expression in healthy murine liver tissue and under inflammatory conditions in vivo. RESULTS: Adiponectin mRNA was readily detectable in healthy liver tissue and further increased in ConA-mediated acute liver failure. Adiponectin protein expression was mainly found in hepatic endothelial cells. In vitro adiponectin mRNA expression was detectable in several cell types, including primary hepatic sinusoidal endothelial cells, stellate cells, and macrophages. Mice pretreated with adiponectin before ConA administration developed reduced hepatic injury as shown by decreased release of transaminases and reduced hepatocellular apoptotis. Of note, TNF-alpha levels were not affected by adiponectin, whereas IL-10 production was increased. Neutralisation of IL-10 diminished the protective effect of adiponectin. CONCLUSIONS: Adiponectin expression is up-regulated in ConA-mediated acute liver failure. Therefore, adiponectin might play a role in the control and limitation of inflammation in the liver. Moreover, our data suggest a role for IL-10 in adiponectin-mediated hepatoprotection

Foraging behaviour of wild impala (Aepyceros melampus) and Burchell's zebra (Equus burchelli) in relation to sward height

Foraging behaviour plays a key role in the interaction between herbivores and vegetation, their predominant food source. Understanding this interaction is crucial to providing information that is useful for conservation of herbivores. The objective of this study was to determine how sward height influences functional response and movement patterns of free ranging wild impala and zebra at the Kenya Wildlife Service Training Institute. The study was conducted for 3 months. Sward height is an important parameter that indicates how intensive a sward has been grazed and it influences intake rate through its effect on bite size. Bite size, instantaneous intake rate, specific mass intake rate and feeding station interval for impala and zebra increased with sward height. Sward height in combination with an animal's sex was found to have a profound effect on specific mass intake rate in impala. Zebra had a longer feeding station interval and lower stepping rate in tall swards compared to impala. Despite differences in their specific body mass and digestive strategies, impala and zebra maximized their intake rates in tall swards as a trade-off among the swards. Tall swards are therefore critical in the study area and should be protected from bush encroachment which is a persistent problem. 2017 John Wiley & Sons Ltd

INSIG1 influences obesity-related hypertriglyceridemia in humans

In our analysis of a quantitative trait locus (QTL) for plasma triglyceride (TG) levels [logarithm of odds (LOD) = 3.7] on human chromosome 7q36, we examined 29 single nucleotide polymorphisms (SNPs) across INSIG1, a biological candidate gene in the region. Insulin-induced genes (INSIGs) are feedback mediators of cholesterol and fatty acid synthesis in animals, but their role in human lipid regulation is unclear. In our cohort, the INSIG1 promoter SNP rs2721 was associated with TG levels (P = 2 × 10−3 in 1,560 individuals of the original linkage cohort, P = 8 × 10−4 in 920 unrelated individuals of the replication cohort, combined P = 9.9 × 10−6). Individuals homozygous for the T allele had 9% higher TG levels and 2-fold lower expression of INSIG1 in surgical liver biopsy samples when compared with individuals homozygous for the G allele. Also, the T allele showed additional binding of nuclear proteins from HepG2 liver cells in gel shift assays. Finally, the variant rs7566605 in INSIG2, the only homolog of INSIG1, enhances the effect of rs2721 (P = 0.00117). The variant rs2721 alone explains 5.4% of the observed linkage in our cohort, suggesting that additional, yet-undiscovered genes and sequence variants in the QTL interval also contribute to alterations in TG levels in humans

Spin dynamics of Mn12-acetate in the thermally-activated tunneling regime: ac-susceptibility and magnetization relaxation

In this work, we study the spin dynamics of Mn12-acetate molecules in the regime of thermally assisted tunneling. In particular, we describe the system in the presence of a strong transverse magnetic field. Similar to recent experiments, the relaxation time/rate is found to display a series of resonances; their Lorentzian shape is found to stem from the tunneling. The dynamic susceptibility $\chi(w)$ is calculated starting from the microscopic Hamiltonian and the resonant structure manifests itself also in $\chi(w)$. Similar to recent results reported on another molecular magnet, Fe8, we find oscillations of the relaxation rate as a function of the transverse magnetic field when the field is directed along a hard axis of the molecules. This phenomenon is attributed to the interference of the geometrical or Berry phase. We propose susceptibility experiments to be carried out for strong transverse magnetic fields to study of these oscillations and for a better resolution of the sharp satellite peaks in the relaxation rates.Comment: 22 pages, 23 figures; submitted to Phys. Rev. B; citations/references adde

Gut-directed hypnotherapy in children with irritable bowel syndrome or functional abdominal pain (syndrome): A randomized controlled trial on self exercises at home using CD versus individual therapy by qualified therapists

Background: Irritable bowel syndrome (IBS) and functional abdominal pain (syndrome) (FAP(S)) are common pediatric disorders, characterized by chronic or recurrent abdominal pain. Treatment is challenging, especially in children with persisting symptoms. Gut-directed hypnotherapy (HT) performed by a therapist has been shown to be effective in these children, but is still unavailable to many children due to costs, a lack of qualified child-hypnotherapists and because it requires a significant investment of time by child and parent(s). Home-based hypnotherapy by means of exercises on CD has been shown effective as well, and has potential benefits, such as lower costs and less time investment. The aim of this randomized controlled trial (RCT) is to compare cost-effectiveness of individual HT performed by a qualified therapist with HT by means of CD recorded self-exercises at home in children with IBS or FAP(S).Methods/Design: 260 children, aged 8-18 years with IBS or FAP(S) according to Rome III criteria are included in this currently conducted RCT with a follow-up period of one year. Children are randomized to either 6 sessions of individual HT given by a qualified therapist over a 3-month period or HT through self-exercises at home with CD for 3 months.The primary outcome is the proportion of patients in which treatment is successful at the end of treatment and after one year follow-up. Treatment success is defined as at least 50% reduction in both abdominal pain frequency and intensity scores. Secondary outcomes include adequate relief, cost-effectiveness an

Anti-inflammatory effects of hepatocyte growth factor: induction of interleukin-1 receptor antagonist

Hepatocyte growth factor (HGF) prevents liver failure in various animal models including endotoxin-induced acute liver failure. We were interested to find out whether human HGF exerts anti-inflammatory effects by modulation of cytokine synthesis. Therefore, human HepG2 cells were cultured with increasing concentrations of HGF. HGF dose-dependently upregulated the production of interleukin-1 receptor antagonist (IL-1Ra). Incubation of HepG2 cells with interleukin-1beta (IL-1beta) caused an increase in IL-1Ra levels, while interleukin-6 (IL-6) had no effect on IL-1Ra synthesis. Co-stimulation of HepG2 cells with HGF + IL-1beta resulted in a synergistic effect on IL-1Ra mRNA and protein expression. Stimulation of freshly isolated mouse hepatocytes from male C57 BL/6 mice with HGF increased IL-1Ra mRNA and protein synthesis dose-dependently. A co-stimulation with HGF and IL-1beta had a synergistic effect on IL-1Ra mRNA expression but only a partially additive effect on IL-1Ra protein synthesis. HGF-induced IL-1Ra production was significantly decreased by the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Accordingly, HGF stimulation specifically increased MAPK-dependent signalling pathway (p42/44). In contrast, in preactivated PBMC mRNA expression and protein synthesis of IL-1Ra, interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) were unaffected after stimulation with HGF. In conclusion, our data suggest that HGF exerts anti-inflammatory effects by modulating the signal transduction cascade leading to increased expression of IL-1Ra, which might explain the protective and regenerative properties of this cytokine in animal models of liver failure

The status of GEO 600

The GEO 600 laser interferometer with 600m armlength is part of a worldwide network of gravitational wave detectors. GEO 600 is unique in having advanced multiple pendulum suspensions with a monolithic last stage and in employing a signal recycled optical design. This paper describes the recent commissioning of the interferometer and its operation in signal recycled mode