Lactobacillus acidophilus Metabolizes Dietary Plant Glucosides and Externalizes Their Bioactive Phytochemicals

ABSTRACT Therapeutically active glycosylated phytochemicals are ubiquitous in the human diet. The human gut microbiota (HGM) modulates the bioactivities of these compounds, which consequently affect host physiology and microbiota composition. Despite a significant impact on human health, the key players and the underpinning mechanisms of this interplay remain uncharacterized. Here, we demonstrate the growth of Lactobacillus acidophilus on mono- and diglucosyl dietary plant glycosides (PGs) possessing small aromatic aglycones. Transcriptional analysis revealed the upregulation of host interaction genes and identified two loci that encode phosphotransferase system (PTS) transporters and phospho-β-glucosidases, which mediate the uptake and deglucosylation of these compounds, respectively. Inactivating these transport and hydrolysis genes abolished or severely reduced growth on PG, establishing the specificity of the loci to distinct groups of PGs. Following intracellular deglucosylation, the aglycones of PGs are externalized, rendering them available for absorption by the host or for further modification by other microbiota taxa. The PG utilization loci are conserved in L. acidophilus and closely related lactobacilli, in correlation with versatile growth on these compounds. Growth on the tested PG appeared more common among human gut lactobacilli than among counterparts from other ecologic niches. The PGs that supported the growth of L. acidophilus were utilized poorly or not at all by other common HGM strains, underscoring the metabolic specialization of L. acidophilus. These findings highlight the role of human gut L. acidophilus and select lactobacilli in the bioconversion of glycoconjugated phytochemicals, which is likely to have an important impact on the HGM and human host. IMPORTANCE Thousands of therapeutically active plant-derived compounds are widely present in berries, fruits, nuts, and beverages like tea and wine. The bioactivity and bioavailability of these compounds, which are typically glycosylated, are altered by microbial bioconversions in the human gut. Remarkably, little is known about the bioconversion of PGs by the gut microbial community, despite the significance of this metabolic facet to human health. Our work provides the first molecular insights into the metabolic routes of diet relevant and therapeutically active PGs by Lactobacillus acidophilus and related human gut lactobacilli. This taxonomic group is adept at metabolizing the glucoside moieties of select PG and externalizes their aglycones. The study highlights an important role of lactobacilli in the bioconversion of dietary PG and presents a framework from which to derive molecular insights into their metabolism by members of the human gut microbiota

Reflexive and volitional saccadic eye movements and their changes in age and progressive supranuclear palsy

BACKGROUND AND OBJECTIVES: Saccades, rapid movements of the eyes towards a visual or remembered target, are useful in understanding the healthy brain and the pathology of neurological conditions such as progressive supranuclear palsy (PSP). We set out to investigate the parameters of horizontal reflexive and volitional saccades, both visually guided and memory-guided, over a 1 min epoch in healthy individuals and PSP patients. METHODS: An experimental paradigm tested reflexive, volitional visually guided, and volitional memory-guided saccades in young healthy controls (n = 14; 20-31 years), PSP patients (n = 11; 46-75 years) and older age-matched healthy controls (n = 6; 56-71 years). The accuracy and velocity of saccades was recorded using an EyeBrain T2® video eye tracker and analyses performed using the MyEyeAnalysis® software. Two-way analysis of variance (ANOVA) was used to identify significant effects (p < 0.01) between young and older controls to investigate the effects of ageing upon saccades, and between PSP patients and age-matched controls to study the effects of PSP upon saccades. RESULTS: In both healthy individuals and PSP patients, volitional saccades are slower and less accurate than reflexive saccades. In PSP patients, accuracy is lower across all saccade types compared to age-matched controls, but velocity is lower only for reflexive saccades. Crucially, there is no change in accuracy or velocity of consecutive saccades over short (one-minute) timescales in controls or PSP patients. CONCLUSIONS: Velocity and accuracy of saccades in PSP does not decrease over one-minute timescales, contrary to that previously observed in Parkinson's Disease (PD), suggesting a potential clinical biomarker for the distinction of PSP from PD

MAPT-Associated Familial Progressive Supranuclear Palsy with Typical Corticobasal Degeneration Neuropathology: A Clinicopathological Report

Corticobasal degeneration (CBD) is a rare, 4-repeat (4R) tauopathy characterized by astrocytic plaque neuropathology. Although ~25% of sporadic CBD cases present with progressive supranuclear palsy-Richardson's syndrome (PSP-RS),1 only one other case of microtubule-associated protein tau gene (MAPT)- related CBD with a PSP-like phenotype has been reported.2 We aim to highlight important issues regarding the classification of MAPT-associated tauopathies and the implications for clinical research

Lifetime of d-holes at Cu surfaces: Theory and experiment

We have investigated the hole dynamics at copper surfaces by high-resolution angle-resolved photoemission experiments and many-body quasiparticle GW calculations. Large deviations from a free-electron-like picture are observed both in the magnitude and the energy dependence of the lifetimes, with a clear indication that holes exhibit longer lifetimes than electrons with the same excitation energy. Our calculations show that the small overlap of d- and sp-states below the Fermi level is responsible for the observed enhancement. Although there is qualitative good agreement of our theoretical predictions and the measured lifetimes, there still exist some discrepancies pointing to the need of a better description of the actual band structure of the solid.Comment: 15 pages, 7 figures, 1 table, to appear in Phys. Rev.

Role of bulk and surface phonons in the decay of metal surface states

We present a comprehensive theoretical investigation of the electron-phonon contribution to the lifetime broadening of the surface states on Cu(111) and Ag(111), in comparison with high-resolution photoemission results. The calculations, including electron and phonon states of the bulk and the surface, resolve the relative importance of the Rayleigh mode, being dominant for the lifetime at small hole binding energies. Including the electron-electron interaction, the theoretical results are in excellent agreement with the measured binding energy and temperature dependent lifetime broadening.Comment: 4 pages, 3 figure

A very conscientious brand: A case study of the BBC's current affairs series Panorama

The reputation of British current affairs and documentary series such as the BBC's Panorama, Channel 4’s Dispatches or the now defunct Granada series World in Action have rested on an image of conscientious ‘public service’. These popular, long running series have, at various points in their history, acted as the ‘conscience of the nation’, seeking to expose social injustice, investigate misdemeanours by the powerful and take on venal or corrupt vested interest. The BBC’s flagship current affairs series Panorama is Britain’s longest running television programme and, according to the Panorama website, ‘the world’s longest running investigative TV show’. It has provided a template for other current affairs series both in Britain, Europe and around the world while undergoing several transformations in form and style since its launch in 1953, the latest and arguably most dramatic being in 2007. This article will chart the development of Panorama as a distinctive, ‘flagship' current affairs series over six decades. It will attempt to answer why the Panorama brand has survived so long, while so many other notable current affairs series have not. Using research and material from Bournemouth University’s Panorama Archive, the Video Active website, the BFI and other European archives this article explores the development of an iconic current affairs series that has, at different stages in its history, proved a template for other news and current affairs programmes. Various breaks and continuities are highlighted in Panorama’s history and identity, and an attempt will be made to characterise and specify the Panorama ‘brand’ and pinpoint the series’ successes and failures in reinventing itself in a rapidly changing media context

MRI of the lung (3/3)-current applications and future perspectives

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations

Early prediction of response to radiotherapy and androgen-deprivation therapy in prostate cancer by repeated functional MRI: a preclinical study

<p>Abstract</p> <p>Background</p> <p>In modern cancer medicine, morphological magnetic resonance imaging (MRI) is routinely used in diagnostics, treatment planning and assessment of therapeutic efficacy. During the past decade, functional imaging techniques like diffusion-weighted (DW) MRI and dynamic contrast-enhanced (DCE) MRI have increasingly been included into imaging protocols, allowing extraction of intratumoral information of underlying vascular, molecular and physiological mechanisms, not available in morphological images. Separately, pre-treatment and early changes in functional parameters obtained from DWMRI and DCEMRI have shown potential in predicting therapy response. We hypothesized that the combination of several functional parameters increased the predictive power.</p> <p>Methods</p> <p>We challenged this hypothesis by using an artificial neural network (ANN) approach, exploiting nonlinear relationships between individual variables, which is particularly suitable in treatment response prediction involving complex cancer data. A clinical scenario was elicited by using 32 mice with human prostate carcinoma xenografts receiving combinations of androgen-deprivation therapy and/or radiotherapy. Pre-radiation and on days 1 and 9 following radiation three repeated DWMRI and DCEMRI acquisitions enabled derivation of the apparent diffusion coefficient (ADC) and the vascular biomarker <it>K</it>^trans, which together with tumor volumes and the established biomarker prostate-specific antigen (PSA), were used as inputs to a back propagation neural network, independently and combined, in order to explore their feasibility of predicting individual treatment response measured as 30 days post-RT tumor volumes.</p> <p>Results</p> <p>ADC, volumes and PSA as inputs to the model revealed a correlation coefficient of 0.54 (p < 0.001) between predicted and measured treatment response, while <it>K</it>^trans, volumes and PSA gave a correlation coefficient of 0.66 (p < 0.001). The combination of all parameters (ADC, <it>K</it>^trans, volumes, PSA) successfully predicted treatment response with a correlation coefficient of 0.85 (p < 0.001).</p> <p>Conclusions</p> <p>We have in a preclinical investigation showed that the combination of early changes in several functional MRI parameters provides additional information about therapy response. If such an approach could be clinically validated, it may become a tool to help identifying non-responding patients early in treatment, allowing these patients to be considered for alternative treatment strategies, and, thus, providing a contribution to the development of individualized cancer therapy.</p

A BioBrick compatible strategy for genetic modification of plants

Background: Plant biotechnology can be leveraged to produce food, fuel, medicine, and materials. Standardized methods advocated by the synthetic biology community can accelerate the plant design cycle, ultimately making plant engineering more widely accessible to bioengineers who can contribute diverse creative input to the design process. Results: This paper presents work done largely by undergraduate students participating in the 2010 International Genetically Engineered Machines (iGEM) competition. Described here is a framework for engineering the model plant Arabidopsis thaliana with standardized, BioBrick compatible vectors and parts available through the Registry of Standard Biological Parts (http://www.partsregistry.org). This system was used to engineer a proof-of-concept plant that exogenously expresses the taste-inverting protein miraculin. Conclusions: Our work is intended to encourage future iGEM teams and other synthetic biologists to use plants as a genetic chassis. Our workflow simplifies the use of standardized parts in plant systems, allowing the construction and expression of heterologous genes in plants within the timeframe allotted for typical iGEM projects.Molecular and Cellular Biolog