Global patterns of β-diversity along the phylogenetic time-scale : the role of climate and plate tectonics

Aim: We aimed to assess the relative influence of the historical and contemporary processes determining global patterns of current \u3b2-diversity. Specifically, we quantified the relative effects of contemporary climate and historical plate tectonics on \u3b2-diversity at different phylogenetic scales. Location: Global. Time Period: Contemporaneous. Major taxa studied: Mammals and birds. Methods: We analysed the current \u3b2-diversity patterns of birds and mammal assemblages at sequential depths in the phylogeny, that is, from the tips to deeper branches. This was done by slicing bird and mammal phylogenetic trees into 66 time slices of 1 Ma (from 0 to 65 Ma) and recording the branches within each slice. Using global distribution data, we defined the branches\u2019 geographical distribution as the union of the corresponding downstream species distributions. For each time slice, we (a) computed pairwise \u3b2-diversity across all the grid cells for the whole world and (b) estimated the correlation between this \u3b2-diversity matrix and contemporary climatic and geographical distances, and past geological distances, a proxy for plate tectonics. Results: Contemporary climate best explained the \u3b2-diversity of shallow branches (i.e., species). For mammals, the geographical isolation of landmasses generated by plate tectonics best explained the \u3b2-diversity of deeper branches, whereas the effect of past isolation was weaker for birds. Main conclusions: Our study shows that the relative influence of contemporary climate and plate tectonics on the \u3b2-diversity of bird and mammal assemblages varies along the phylogenetic time-scale. Our phylogenetic time-scale approach is general and flexible enough to be applied to a broad spectrum of study systems and spatial scales

Automated Real-Time Tumor Pharmacokinetic Profiling in 3D Models: A Novel Approach for Personalized Medicine

Cancer treatment often lacks individual dose adaptation, contributing to insufficient efficacy and severe side effects. Thus, personalized approaches are highly desired. Although various analytical techniques are established to determine drug levels in preclinical models, they are limited in the automated real-time acquisition of pharmacokinetic profiles. Therefore, an online UHPLC-MS/MS system for quantitation of drug concentrations within 3D tumor oral mucosa models was generated. The integration of sampling ports into the 3D tumor models and their culture inside the autosampler allowed for real-time pharmacokinetic profiling without additional sample preparation. Docetaxel quantitation was validated according to EMA guidelines. The tumor models recapitulated the morphology of head-and-neck cancer and the dose-dependent tumor reduction following docetaxel treatment. The administration of four different docetaxel concentrations resulted in comparable courses of concentration versus time curves for 96 h. In conclusion, this proof-of-concept study demonstrated the feasibility of real-time monitoring of drug levels in 3D tumor models without any sample preparation. The inclusion of patient-derived tumor cells into our models may further optimize the pharmacotherapy of cancer patients by efficiently delivering personalized data of the target tissue

Salience versus magnitude in the measurement of the cortisol awakening response

Pulsatile ultradian secretion of cortisol, rarely studied in salivary data, has functional importance in hypothalamic pituitary adrenal (HPA) axis regulation. The first daily ultradian episode, the cortisol awakening response (CAR), was examined in healthy adults, in 5-min secretion rates of salivary cortisol from electronically monitored awakening time to 1.25 h. Aggregated rates revealed a cubic trend, with wave-length of almost exactly 1 h, as predicted from known ultradian periodicity. Peak secretion rate occurred 20-min post-awakening. Peak (20-min) to trough (59-min) amplitude (PTA) expressed a salient signal shape. Rates rose steeply to and from peak, and major secretion was packaged into a few 5-min intervals, inconsistent with normal or uniform distribution of 5-min rates, but consistent with known pulsatile cortisol delivery. Null hypotheses asserting normal or uniform distributions were rejected. Maximal rates overwhelmingly occurred before and minimal rates after 30-mins, with degree of extremity at each polarity significantly positively correlated. To demonstrate utility and reliability of PTA estimation in a clinically relevant domain, re- analyses of a previously published study were conducted. Data from only three saliva samples were used, given importance of cost considerations for many CAR researchers. Difference between mean rates before and after 30-min yielded a simple salience index, highly correlated with PTA derived from full 5-min interval data. CAR salience performed significantly better than traditional AUCi magnitude in discriminating control cases (higher inferred amplitude) and cases with Seasonal Affective Disorder (lower inferred amplitude). Evidence suggested that low AUCi may be more sensitive in identifying within-subject changes (e.g. more depressed mood in winter among SAD cases) and low CAR salience better at revealing enduring between-subjects associations (e.g. underlying disorder vulnerability). Since both PTA salience and AUCi magnitude can be analysed and compared using exactly the same data from the same commonly used saliva sampling points, further research is warranted into the importance of individual differences in patterns of cortisol delivery, not just how much is delivered

The Herpes Simplex Virus-1 Transactivator Infected Cell Protein-4 Drives VEGF-A Dependent Neovascularization

Herpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic privilege and extensive neovascularization driven by vascular endothelial growth factor-A (VEGF-A). In the current study, we identify HSV-1 infected cells as the dominant source of VEGF-A during acute infection, and VEGF-A transcription did not require TLR signaling or MAP kinase activation. Rather than being an innate response to the pathogen, VEGF-A transcription was directly activated by the HSV-1 encoded immediate early transcription factor, ICP4. ICP4 bound the proximal human VEGF-A promoter and was sufficient to promote transcription. Transcriptional activation also required cis GC-box elements common to the VEGF-A promoter and HSV-1 early genes. Our results suggest that the neovascularization characteristic of ocular HSV-1 disease is a direct result of HSV-1's major transcriptional regulator, ICP4, and similarities between the VEGF-A promoter and those of HSV-1 early genes

Synthesis of fluorosugar reagents for the construction of well-defined fluoroglycoproteins.

2-Deoxy-2-fluoroglycosyl iodides are privileged glycosyl donors for the stereoselective preparation of 1-Nu-β-fluorosugars, which are useful reagents for chemical site-selective protein glycosylation. Ready access to such β-fluorosugars enables the mild and efficient construction of well-defined fluoroglycoproteins.We thank the European Commission (Marie Curie CIG, O.B. and G.J.L.B.), MICINN, Spain (Juan de la Cierva Fellowship, O.B.), MINECO, Spain (CTQ2011-22872BQU) and Generalitat de Catalunya (M.S.) for generous financial support. We also thank Mr. Adrià Cardona-Benages (URV) for technical assis-tance. G.J.L.B. thanks the Royal Society (University Research Fellowship), Fundação para a Ciência a Tecnologia, Portugal (FCT Investigator), and the EPSRC for funding.This is the final version of the article. It first appeared from ACS via http://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b01259

Experimental limits on nucleon decay and ΔB=2 processes

Results from the IMB collabration to detect possible proton decay in a salt mine near Cleveland, Ohio are presented. Detection apparatus is described.(AIP)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87900/2/1_1.pd

Product-service systems evolution in the era of Industry 4.0

Funder: Università degli studi di BergamoAbstract: Recent economic transformations have forced companies to redefine their value propositions, increasing traditional product offerings with supplementary services—the so-called Product-Service System (PSS). Among them, the adoption of Industry 4.0 technologies is very common. However, the directions that companies are undertaking to offer new value to their customers in the Industry 4.0 have not yet been investigated in detail. Based on a focus group, this paper contributes to this understanding by identifying the main trajectories that would shape a future scenario in which PSS and Industry 4.0 would merge. In addition, future research directions addressing (a) the transformation of the PSS value chain into a PSS ecosystem, (b) the transformation inside a single company towards becoming a PSS provider, and (c) the digital transformation of the traditional PSS business model are identified