Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver

BACKGROUND: The liver is the central organ for xenobiotic metabolism (XM) and is regulated by nuclear receptors such as CAR and PXR, which control the metabolism of drugs. Here we report that gut microbiota influences liver gene expression and alters xenobiotic metabolism in animals exposed to barbiturates. PRINCIPAL FINDINGS: By comparing hepatic gene expression on microarrays from germfree (GF) and conventionally-raised mice (SPF), we identified a cluster of 112 differentially expressed target genes predominantly connected to xenobiotic metabolism and pathways inhibiting RXR function. These findings were functionally validated by exposing GF and SPF mice to pentobarbital which confirmed that xenobiotic metabolism in GF mice is significantly more efficient (shorter time of anesthesia) when compared to the SPF group. CONCLUSION: Our data demonstrate that gut microbiota modulates hepatic gene expression and function by altering its xenobiotic response to drugs without direct contact with the liver

Scalable multi-particle entanglement of trapped ions

Among the various kinds of entangled states, the 'W state' plays an important role as its entanglement is maximally persistent and robust even under particle loss. Such states are central as a resource in quantum information processing and multiparty quantum communication. Here we report the scalable and deterministic generation of four-, five-, six-, seven- and eight-particle entangled states of the W type with trapped ions. We obtain the maximum possible information on these states by performing full characterization via state tomography, using individual control and detection of the ions. A detailed analysis proves that the entanglement is genuine. The availability of such multiparticle entangled states, together with full information in the form of their density matrices, creates a test-bed for theoretical studies of multiparticle entanglement. Independently, -Greenberger-Horne-Zeilinger- entangled states with up to six ions have been created and analysed in Boulder

The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex

A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein essential for embryonic development, and its dysregulation underlies disorders such as cancer, Alzheimer's disease, and inflammation. ADAM10 is a molecular scissor that proteolytically cleaves the extracellular region from >100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors, and chemokines. ADAM10 has been recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six regulatory tetraspanins, termed TspanC8s. However, it remains unclear to what degree ADAM10 function critically depends on a TspanC8 partner, and a lack of monoclonal antibodies specific for most TspanC8s has hindered investigation of this question. To address this knowledge gap, here we designed an immunogen to generate the first monoclonal antibodies targeting Tspan15, a model TspanC8. The immunogen was created in an ADAM10-knockout mouse cell line stably overexpressing human Tspan15, because we hypothesized that expression in this cell line would expose epitopes that are normally blocked by ADAM10. Following immunization of mice, this immunogen strategy generated four Tspan15 antibodies. Using these antibodies, we show that endogenous Tspan15 and ADAM10 co-localize on the cell surface, that ADAM10 is the principal Tspan15-interacting protein, that endogenous Tspan15 expression requires ADAM10 in cell lines and primary cells, and that a synthetic ADAM10/Tspan15 fusion protein is a functional scissor. Furthermore, two of the four antibodies impaired ADAM10/Tspan15 activity. These findings suggest that Tspan15 directly interacts with ADAM10 in a functional scissor complex

Evaluation of the Frails' Fall Efficacy by Comparing Treatments (EFFECT) on reducing fall and fear of fall in moderately frail older adults: study protocol for a randomised control trial

<p>Abstract</p> <p>Background</p> <p>Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo^®Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo^®Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline.</p> <p>Methods</p> <p>This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments.</p> <p>Discussions</p> <p>The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12610000576022.aspx">ACTRN12610000576022</a></p

ROS release by PPARβ/δ-null fibroblasts reduces tumor load through epithelial antioxidant response.

Tumor stroma has an active role in the initiation, growth, and propagation of many tumor types by secreting growth factors and modulating redox status of the microenvironment. Although PPARβ/δ in fibroblasts was shown to modulate oxidative stress in the wound microenvironment, there has been no evidence of a similar effect in the tumor stroma. Here, we present evidence of oxidative stress modulation by intestinal stromal PPARβ/δ, using a FSPCre-Pparb/d &lt;sup&gt;-/-&lt;/sup&gt; mouse model and validated it with immortalized cell lines. The FSPCre-Pparb/d &lt;sup&gt;-/-&lt;/sup&gt; mice developed fewer intestinal polyps and survived longer when compared with Pparb/d &lt;sup&gt;fl/fl&lt;/sup&gt; mice. The pre-treatment of FSPCre-Pparb/d &lt;sup&gt;-/-&lt;/sup&gt; and Pparb/d &lt;sup&gt;fl/fl&lt;/sup&gt; with antioxidant N-acetyl-cysteine prior DSS-induced tumorigenesis resulted in lower tumor load. Gene expression analyses implicated an altered oxidative stress processes. Indeed, the FSPCre-Pparb/d &lt;sup&gt;-/-&lt;/sup&gt; intestinal tumors have reduced oxidative stress than Pparb/d &lt;sup&gt;fl/fl&lt;/sup&gt; tumors. Similarly, the colorectal cancer cells and human colon epithelial cells also experienced lower oxidative stress when co-cultured with fibroblasts depleted of PPARβ/δ expression. Therefore, our results establish a role for fibroblast PPARβ/δ in epithelial-mesenchymal communication for ROS homeostasis

Rapid Acoustic Survey for Biodiversity Appraisal

Biodiversity assessment remains one of the most difficult challenges encountered by ecologists and conservation biologists. This task is becoming even more urgent with the current increase of habitat loss. Many methods–from rapid biodiversity assessments (RBA) to all-taxa biodiversity inventories (ATBI)–have been developed for decades to estimate local species richness. However, these methods are costly and invasive. Several animals–birds, mammals, amphibians, fishes and arthropods–produce sounds when moving, communicating or sensing their environment. Here we propose a new concept and method to describe biodiversity. We suggest to forego species or morphospecies identification used by ATBI and RBA respectively but rather to tackle the problem at another evolutionary unit, the community level. We also propose that a part of diversity can be estimated and compared through a rapid acoustic analysis of the sound produced by animal communities. We produced α and β diversity indexes that we first tested with 540 simulated acoustic communities. The α index, which measures acoustic entropy, shows a logarithmic correlation with the number of species within the acoustic community. The β index, which estimates both temporal and spectral dissimilarities, is linearly linked to the number of unshared species between acoustic communities. We then applied both indexes to two closely spaced Tanzanian dry lowland coastal forests. Indexes reveal for this small sample a lower acoustic diversity for the most disturbed forest and acoustic dissimilarities between the two forests suggest that degradation could have significantly decreased and modified community composition. Our results demonstrate for the first time that an indicator of biological diversity can be reliably obtained in a non-invasive way and with a limited sampling effort. This new approach may facilitate the appraisal of animal diversity at large spatial and temporal scales