Biological properties of water-soluble phosphorhydrazone dendrimers

1984-8250Dendrimers are hyperbranched and perfectly defined macromolecules, constituted of branches emanating from a central core in an iterative fashion. Phosphorhydrazone dendrimers constitute a special family of dendrimers, possessing one phosphorus atom at each branching point. The internal structure of these dendrimers is hydrophobic, but hydrophilic terminal groups can induce the solubility of the whole structure in water. Indeed, the properties of these compounds are mainly driven by the type of terminal groups their bear; this is especially true for the biological properties. For instance, positively charged terminal groups are efficient for transfection experiments, as drug carriers, as anti-prion agents, and as inhibitor of the aggregation of Alzheimer's peptides, whereas negatively charged dendrimers have anti-HIV properties and can influence the human immune system, leading to anti-inflammatory properties usable against rheumatoid arthritis. This review will give the most representative examples of the biological properties of water-soluble phosphorhydrazone dendrimers, organized depending on the type of terminal groups they bear

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Planck pre-launch status : The Planck mission

Peer reviewe

Specific vapor sorption properties of phosphorus-containing dendrimers

Specific combination of guest sorption properties was observed for phosphorus-containing dendrimers, which distinguish them from ordinary polymers and clathrate-forming hosts. The sorption capacity for 30 volatile guests, binding reversibility, guest desorption kinetics and guest exchange, glass transition behavior and ability to be plasticized with guest were studied for phosphorus dendrimers of different generations (G1-G4 and G9) using quartz crystal microbalance sensor, FTIR microspectroscopy, atomic force microscopy, simultaneous thermogravimetry and differential scanning calorimetry combined with mass-spectrometry of evolved vapors. The dendrimers were found to have a different selectivity for different homological series of guests, high glass transition points without plasticization with guest even at high temperatures and saturation levels, moderate guest-binding irreversibility and ability both for effective guest exchange and independent guest sorption. These properties constitute an advantage of the studied dendrimers as receptor materials in various applications. © 2011 Elsevier Inc

Dendrimers toward translational nanotherapeutics: concise key step analysis

The goal of nanomedicine is to address specific clinical problems optimally, to fight human diseases, and to find clinical relevance to change clinical practice. Nanomedicine is poised to revolutionize medicine via the development of more precise diagnostic and therapeutic tools. The field of nanomedicine encompasses numerous features and therapeutic disciplines. A plethora of nanomolecular structures have been engineered and developed for therapeutic applications based on their multitasking abilities and the wide functionalization of their core scaffolds and surface groups. Within nanoparticles used for nanomedicine, dendrimers as well polymers have demonstrated strong potential as nanocarriers, therapeutic agents, and imaging contrast agents. In this review, we present and discuss the different criteria and parameters to be addressed to prepare and develop druggable nanoparticles in general and dendrimers in particular. We also describe the major requirements, included in the preclinical and clinical roadmap, for NPs/dendrimers for the preclinical stage to commercialization. Ultimately, we raise the clinical translation of new nanomedicine issues.info:eu-repo/semantics/publishedVersio

Does Charge Carrier Dimensionality Increase in Mixed-Valence Salts of Tetrathiafulvalene-Terminated Dendrimers?

In four new dendrimers terminated by 12 electroactive tetrathiafulvalenyl substituents, the tridimensional character of the inter- and intradendrimeric charge and electron transfer, and hence of the electroconductivity, is evidenced by examination of the electronic spectra of their corresponding neutral state and cation radical, dication, and mixed-valence salts, including a closed-shell anion

Fasciola and fasciolosis in ruminants in Europe: Identifying research needs

18 páginas, 1 figura, 2 tablas.Fasciola hepatica is a trematode parasite with a global distribution, which is responsible for considerable disease and production losses in a range of food producing species. It is also identified by WHO as a re-emerging neglected tropical disease associated with endemic and epidemic outbreaks of disease in human populations. In Europe, F. hepatica is mostly associated with disease in sheep, cattle and goats. This study reviews the most recent advances in our understanding of the transmission, diagnosis, epidemiology and the economic impact of fasciolosis. We also focus on the impact of the spread of resistance to anthelmintics used to control F. hepatica and consider how vaccines might be developed and applied in the context of the immune-modulation driven by the parasite. Several major research gaps are identified which, when addressed, will contribute to providing focussed and where possible, bespoke, advice for farmers on how to integrate stock management and diagnosis with vaccination and/or targeted treatment to more effectively control the parasite in the face of increasing the prevalence of infection and spread of anthelmintic resistance that are likely to be exacerbated by climate change.All authors are members of the Livestock Helminth Research Alliance (LiHRA), whose vision is to improve the health, wealth and productivity of European livestock by providing sustainable helminth control options. This review was commissioned by DISCONTOOLS (www.discontools.eu) as part of the process of identifying research gaps which impinge on effective and sustainable control of fasciolosis in food producing animals in Europe. DJLW, JC, LR, CC, JPA, AMM all received funding from the European Union through the following awards: FPVI‐FOOD‐CT‐200X‐023025‐DELIVER; FPVII‐KBBE‐2011‐5‐288975‐GLOWORM; FPVII‐KBBE‐2010‐4‐265862‐PARAVAC; H2020‐635408‐PARAGONE. DJLW, JEH, NJB received funding from the Biotechnology and Biological Sciences Research Council (BBSRC) through awards: BB/K015591/1 and BBI002480/1, and RJF was supported by BBSRC award BB/M018520/1. MMV was funded by the Spanish “Ramón y Cajal” Programme of the Ministry of Economy and Competitiveness (RYC‐2015‐18368). CC was funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England (PHE) and Liverpool School of Tropical Medicine (LSTM). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or PHE.Peer reviewe

Risk factors for tick attachment in companion animals in Great Britain: a spatiotemporal analysis covering 2014–2021

Abstract Background Ticks are an important driver of veterinary health care, causing irritation and sometimes infection to their hosts. We explored epidemiological and geo-referenced data from &gt; 7 million electronic health records (EHRs) from cats and dogs collected by the Small Animal Veterinary Surveillance Network (SAVSNET) in Great Britain (GB) between 2014 and 2021 to assess the factors affecting tick attachment in an individual and at a spatiotemporal level. Methods EHRs in which ticks were mentioned were identified by text mining; domain experts confirmed those with ticks on the animal. Tick presence/absence records were overlaid with a spatiotemporal series of climate, environment, anthropogenic and host distribution factors to produce a spatiotemporal regression matrix. An ensemble machine learning spatiotemporal model was used to fine-tune hyperparameters for Random Forest, Gradient-boosted Trees and Generalized Linear Model regression algorithms, which were then used to produce a final ensemble meta-learner to predict the probability of tick attachment across GB at a monthly interval and averaged long-term through 2014–2021 at a spatial resolution of 1 km. Individual host factors associated with tick attachment were also assessed by conditional logistic regression on a matched case–control dataset. Results In total, 11,741 consultations were identified in which a tick was recorded. The frequency of tick records was low (0.16% EHRs), suggesting an underestimation of risk. That said, increased odds for tick attachment in cats and dogs were associated with younger adult ages, longer coat length, crossbreeds and unclassified breeds. In cats, males and entire animals had significantly increased odds of recorded tick attachment. The key variables controlling the spatiotemporal risk for tick attachment were climatic (precipitation and temperature) and vegetation type (Enhanced Vegetation Index). Suitable areas for tick attachment were predicted across GB, especially in forests and grassland areas, mainly during summer, particularly in June. Conclusions Our results can inform targeted health messages to owners and veterinary practitioners, identifying those animals, seasons and areas of higher risk for tick attachment and allowing for more tailored prophylaxis to reduce tick burden, inappropriate parasiticide treatment and potentially TBDs in companion animals and humans. Sentinel networks like SAVSNET represent a novel complementary data source to improve our understanding of tick attachment risk for companion animals and as a proxy of risk to humans. Graphical Abstract </jats:sec

The effect of explicit convection on simulated malaria transmission across Africa

Malaria transmission across sub-Saharan Africa is sensitive to rainfall and temperature. Whilst different malaria modelling techniques and climate simulations have been used to predict malaria transmission risk, most of these studies use coarse-resolution climate models. In these models convection, atmospheric vertical motion driven by instability gradients and responsible for heavy rainfall, is parameterised. Over the past decade enhanced computational capabilities have enabled the simulation of high-resolution continental-scale climates with an explicit representation of convection. In this study we use two malaria models, the Liverpool Malaria Model (LMM) and Vector-Borne Disease Community Model of the International Centre for Theoretical Physics (VECTRI), to investigate the effect of explicitly representing convection on simulated malaria transmission. The concluded impact of explicitly representing convection on simulated malaria transmission depends on the chosen malaria model and local climatic conditions. For instance, in the East African highlands, cooler temperatures when explicitly representing convection decreases LMM-predicted malaria transmission risk by approximately 55%, but has a negligible effect in VECTRI simulations. Even though explicitly representing convection improves rainfall characteristics, concluding that explicit convection improves simulated malaria transmission depends on the chosen metric and malaria model. For example, whilst we conclude improvements of 45% and 23% in root mean squared differences of the annual-mean reproduction number and entomological inoculation rate for VECTRI and the LMM respectively, bias-correcting mean climate conditions minimises these improvements. The projected impact of anthropogenic climate change on malaria incidence is also sensitive to the chosen malaria model and representation of convection. The LMM is relatively insensitive to future changes in precipitation intensity, whilst VECTRI predicts increased risk across the Sahel due to enhanced rainfall. We postulate that VECTRI’s enhanced sensitivity to precipitation changes compared to the LMM is due to the inclusion of surface hydrology. Future research should continue assessing the effect of high-resolution climate modelling in impact-based forecasting