Heat in optical tweezers

Laser-induced thermal effects in optically trapped microspheres and single cells have been investigated by Luminescence Thermometry. Thermal spectroscopy has revealed a non-localized temperature distribution around the trap that extends over tens of microns, in agreement with previous theoretical models. Solvent absorption has been identified as the key parameter to determine laser-induced heating, which can be reduced by establishing a continuous fluid flow of the sample. Our experimental results of thermal loading at a variety of wavelengths reveal that an optimum trapping wavelength exists for biological applications close to 820 nm. This has been corroborated by a simultaneous analysis of the spectral dependence of cellular heating and damage in human lymphocytes during optical trapping. Minimum intracellular heating, well below the cytotoxic level (43 °C), has been demonstrated to occur for optical trapping with 820 nm laser radiation, thus avoiding cell damage

Fungal endophytes from arid areas of Andalusia: high potential sources for antifungal and antitumoral agents

Native plant communities from arid areas present distinctive characteristics to survive in extreme conditions. The large number of poorly studied endemic plants represents a unique potential source for the discovery of novel fungal symbionts as well as host-specific endophytes not yet described. The addition of adsorptive polymeric resins in fungal fermentations has been seen to promote the production of new secondary metabolites and is a tool used consistently to generate new compounds with potential biological activities. A total of 349 fungal strains isolated from 63 selected plant species from arid ecosystems located in the southeast of the Iberian Peninsula, were characterized morphologically as well as based on their ITS/28S ribosomal gene sequences. The fungal community isolated was distributed among 19 orders including Basidiomycetes and Ascomycetes, being Pleosporales the most abundant order. In total, 107 different genera were identified being Neocamarosporium the genus most frequently isolated from these plants, followed by Preussia and Alternaria. Strains were grown in four different media in presence and absence of selected resins to promote chemical diversity generation of new secondary metabolites. Fermentation extracts were evaluated, looking for new antifungal activities against plant and human fungal pathogens, as well as, cytotoxic activities against the human liver cancer cell line HepG2. From the 349 isolates tested, 126 (36%) exhibited significant bioactivities including 58 strains with exclusive antifungal properties and 33 strains with exclusive activity against the HepG2 hepatocellular carcinoma cell line. After LCMS analysis, 68 known bioactive secondary metabolites could be identified as produced by 96 strains, and 12 likely unknown compounds were found in a subset of 14 fungal endophytes. The chemical profiles of the differential expression of induced activities were compared. As proof of concept, ten active secondary metabolites only produced in the presence of resins were purified and identified. The structures of three of these compounds were new and herein are elucidated.This work was supported by Fundación MEDINA and the Andalusian Government grant RNM-7987 ‘Sustainable use of plants and their fungal parasites from arid regions of Andalucía for new molecules useful for antifungals and neuroprotectors’

Site-selective protein-modification chemistry for basic biology and drug development.

Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of reactions that enable post-expression modification of proteins at pre-determined sites. These reactions are now used to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to determine their exact biological roles. Labelling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiological parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chemical site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.We thank FCT Portugal (FCT Investigator to G.J.L.B.), the EU (Marie-Curie CIG to G.J.L.B. and Marie-Curie IEF to O.B.) and the EPSRC for funding. G.J.L.B. is a Royal Society University Research Fellow.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nchem.239

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p

Polymeric Nanoparticles

Self-assembling polymers, which are either amphiphilic block copolymers with hydrophobic and hydrophilic blocks, hydrophilic polymer backbones substituted with hydrophobic units or polymers with a low aqueous solubility, may all be used to prepare aqueous dispersions of polymeric nanoparticles. The amphiphilic variants form polymeric micelles and polymeric bilayer vesicles. The hydrophobic polymers form dense amorphous polymeric particles. Polymeric particles, of whichever nature, may be loaded with hydrophobic and hydrophilic drugs, and the bioavailability of the drug compound is altered by this encapsulation within a polymeric nanoparticle. This simple concept has been exploited heavily to yield enhancements in oral, tumour and brain bioavailability and some of these polymeric nanoparticle formulations have undergone clinical testing and even been commercialised, e.g. the nanoparticle paclitaxel formulation AbraxaneNon peer reviewe

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study

Background: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Methods: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≥3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Results: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). Conclusions: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health. Trial registration: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated FIS projects led by Jordi Salas-Salvadó and Josep Vidal, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-PLUS grant to Jordi Salas-Salvadó; the European Research Council grant (Advanced Research Grant 2013–2019; 340918) to Miguel Ángel Martínez-Gonzalez; the Recercaixa grant to Jordi Salas-Salvadó (2013ACUP00194); grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016; PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; Grant of support to research groups no. 35/2011 (Balearic Islands Gov. & FEDER funds) to Catalina M. Mascaró and Josep A. Tur; FPU Programme, PhD fellowship (Spanish Ministry of Science, Innovation & Universities) to Catalina M. Mascaró; the Astra Zeneca Young Investigators Award in Category of Obesity and Diabetes 2017 to Dora Romaguera; Juan de la Cierva-formación research grant (FJCI-2015-24058) of the Spanish Ministry of Economy, Industry and Competitiveness and European Social Funds to Jadwiga Konieczna; the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 ofthe Balearic Islands) to Jadwiga Konieczna. JR17/00022 contract to Olga Castaner from ISCIII. CIBERobn (Centros de Investigación Biomedica en Red: Obesidad y Nutrición), CIBEResp (Centros de Investigación Biomedica en Red: Epidemiología y Salud Publica) and CIBERdem (Centros de Investigación Biomedica en Red: Diabetes y Enfermedades). None of the funding sources took part in the design, collection, analysis or interpretation of the data and in writing the manuscript, or in the decision to submit the manuscript for publication