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Hybrid architectures which combine a MIP with an immobilized affinity ligand or a biocatalyst sum up the advantages of both components. In this paper, hybrid architectures combining a layer of a molecularly imprinted electropolymer with a mini-enzyme or a self-assembled monolayer will be presented. (i) Microperoxidase-11 (MP-11) catalyzed oxidation of the drug aminopyrine on a product-imprinted sublayer: The peroxide dependent conversion of the analyte aminopyrine takes place in the MP-11 containing layer on top of a product-imprinted electropolymer on the indicator electrode. The hierarchical architecture resulted in the elimination of interfering signals for ascorbic acid and uric acid. An advantage of the new hierarchical structure is the separation of MIP formation by electropolymerization and immobilization of the catalyst. In this way it was for the first time possible to integrate an enzyme with a MIP layer in a sensor configuration. This combination has the potential to be transferred to other enzymes, e.g. P450, opening the way to clinically important analytes. (ii) Epitope-imprinted poly-scopoletin layer for binding of the C-terminal peptide and cytochrome c (Cyt c): The MIP binds both the target peptide and the parent protein almost eight times stronger than the non-imprinted polymer with affinities in the lower micromolar range. Exchange of only one amino acid in the peptide decreases the binding by a factor of five. (iii) MUA-poly-scopoletin MIP for cytochrome c: Cyt c bound to the MIP covered gold electrode exhibits direct electron transfer with a redox potential and rate constant typical for the native protein. The MIP cover layer suppresses the displacement of the target protein by BSA or myoglobin. The combination of protein imprinted polymers with an efficient electron transfer is a new concept for characterizing electroactive proteins such as Cyt c. The competition with other proteins shows that the MIP binds its target Cyt c preferentially and that molecular shape and the charge of protein determine the binding of interfering proteins.
In recent years, core/shell nanohybrids containing a nanoparticle core and a distinct surrounding shell of polymer brushes have received extensive attention in nanoelectronics, nanophotonics, catalysis, nanopatterning, drug delivery, biosensing, and many others. From the large variety of existing polymerization methods on the one hand and strategies for grafting onto nanoparticle surfaces on the other hand, the combination of grafting-from with controlled radical polymerization (CRP) techniques has turned out to be the best suited for synthesizing these well-defined core/shell nanohybrids and is known as surface-initiated CRP. Most common among these are surface-initiated atom transfer radical polymerization (ATRP), surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization, and surface-initiated nitroxide-mediated polymerization (NMP). This review highlights the state of the art of growing polymers from nanoparticles using surface-initiated CRP techniques. We focus on mechanistic aspects, synthetic procedures, and the formation of complex architectures as well as novel properties. From the vast number of examples of nanoparticle/polymer hybrids formed by surface-initiated CRP techniques, we present nanohybrid formation from the particularly important and most studied silica nanoparticles, gold nanocrystals, and proteins which can be regarded as bionanoparticles.
Background: Castilian-Spanish, Catalan, Galician, and European Portuguese are the most widely spoken languages of the Ibero-Romance group. An increasing number of authors have addressed the impact of aphasia on the morphosyntax of these varieties. However, accurate linguistic characterisations are scarce and the different sources of data have not been yet compiled.Aims: To stimulate state-of-the-art research, we provided a comprehensive summary of morphosyntactic aspects of Ibero-Romance and a review of how these are affected in non-fluent aphasia. The topics we dealt with are the use of verb argument structure and morphology, sentential negation and word order, definite articles, personal and reflexive pronouns, passives, topicalised constructions, questions, and relative clauses.Methods & Procedures: An exhaustive fieldwork and search of PubMed, Web of Science, and Medline records were performed to retrieve studies focused on morphosyntactic issues concerning the Ibero-Romance varieties. A total of 27 studies produced by 46 authors of varying background emerged. We did not review studies of category-specific deficits and aspects related to bilingual aphasia, although we assume that most speakers of Galician and Catalan are bilingual. Studies of spontaneous speech were included when no controlled experimental tasks were available.Outcomes & Results: The morphosyntactic commonalities of Ibero-Romance have been tackled from different theoretical perspectives. There exist asymmetries in findings which we explain with the use of different tasks (and task complexity) and individual differences between participants.Conclusions: Discourse-linking factors as well as deviations from the canonical pattern are recurrent answers to these asymmetries. A comprehensive theory of impairments in non-fluent aphasia integrating relevant aspects of both structural and processing accounts seems necessary.
Challenges in secondary prevention of cardiovascular diseases A review of the current practice
(2015)
With the changing demography of populations and increasing prevalence of co-morbidity, frail patients and more complex cardiac conditions, the modern medicine is facing novel challenges leading to rapid innovation where evidence and experiences are lacking. This scenario is also evident in cardiovascular disease prevention, which continuously needs to accommodate its ever changing strategies, settings, and goals. The present paper summarises actual challenges of secondary prevention, and discusses how this intervention should not only be effective but also efficient. By this way the paper tries to bridge the gaps between research and real-world findings and thereby may find ways to improve standard care. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
tRNAs, nexus molecules between mRNAs and proteins, have a central role in translation. Recent discoveries have revealed unprecedented complexity of tRNA biosynthesis, modification patterns, regulation and function. In this Review, we present emerging concepts regarding how tRNA abundance is dynamically regulated and how tRNAs (and their nucleolytic fragments) are centrally involved in stress signalling and adaptive translation, operating across a wide range of timescales. Mutations in tRNAs or in genes affecting tRNA biogenesis are also linked to complex human diseases with surprising heterogeneity in tissue vulnerability, and we highlight cell-specific aspects that modulate the disease penetrance of tRNA-based pathologies.
Oxidative stress causes dramatic changes in the expression levels of many genes. The formation of a functional protein through successful mRNA translation is central to a coordinated cellular response. To what extent the response towards reactive oxygen species (ROS) is regulated at the translational level is poorly understood. Here we analysed leaf- and tissue-specific translatomes using a set of transgenic Arabidopsis thaliana lines expressing a FLAG-tagged ribosomal protein to immunopurify polysome-bound mRNAs before and after oxidative stress. We determined transcript levels of 171 ROS-responsive genes upon paraquat treatment, which causes formation of superoxide radicals, at the whole-organ level. Furthermore, the translation of mRNAs was determined for five cell types: mesophyll, bundle sheath, phloem companion, epidermal and guard cells. Mesophyll and bundle sheath cells showed the strongest response to paraquat treatment. Interestingly, several ROS-responsive transcription factors displayed cell type-specific translation patterns, while others were translated in all cell types. In part, cell type-specific translation could be explained by the length of the 5-untranslated region (5-UTR) and the presence of upstream open reading frames (uORFs). Our analysis reveals insights into the translational regulation of ROS-responsive genes, which is important to understanding cell-specific responses and functions during oxidative stress.
The study illustrates the response of different Arabidopsis thaliana leaf cells and tissues to oxidative stress at the translational level, an aspect of reactive oxygen species (ROS) biology that has been little studied in the past. Our data reveal insights into how translational regulation of ROS-responsive genes is fine-tuned at the cellular level, a phenomenon contributing to the integrated physiological response of leaves to stresses involving changes in ROS levels.
Islands as model systems in ecology and evolution: prospects fifty years after MacArthur-Wilson
(2015)
The study of islands as model systems has played an important role in the development of evolutionary and ecological theory. The 50th anniversary of MacArthur and Wilson's (December 1963) article, An equilibrium theory of insular zoogeography', was a recent milestone for this theme. Since 1963, island systems have provided new insights into the formation of ecological communities. Here, building on such developments, we highlight prospects for research on islands to improve our understanding of the ecology and evolution of communities in general. Throughout, we emphasise how attributes of islands combine to provide unusual research opportunities, the implications of which stretch far beyond islands. Molecular tools and increasing data acquisition now permit re-assessment of some fundamental issues that interested MacArthur and Wilson. These include the formation of ecological networks, species abundance distributions, and the contribution of evolution to community assembly. We also extend our prospects to other fields of ecology and evolution - understanding ecosystem functioning, speciation and diversification - frequently employing assets of oceanic islands in inferring the geographic area within which evolution has occurred, and potential barriers to gene flow. Although island-based theory is continually being enriched, incorporating non-equilibrium dynamics is identified as a major challenge for the future.
During the course of their ontogenesis plants are continuously exposed to a large variety of abiotic stress factors which can damage tissues and jeopardize the survival of the organism unless properly countered. While animals can simply escape and thus evade stressors, plants as sessile organisms have developed complex strategies to withstand them. When the intensity of a detrimental factor is high, one of the defense programs employed by plants is the induction of programmed cell death (PCD). This is an active, genetically controlled process which is initiated to isolate and remove damaged tissues thereby ensuring the survival of the organism. The mechanism of PCD induction usually includes an increase in the levels of reactive oxygen species (ROS) which are utilized as mediators of the stress signal. Abiotic stress-induced PCD is not only a process of fundamental biological importance, but also of considerable interest to agricultural practice as it has the potential to significantly influence crop yield. Therefore, numerous scientific enterprises have focused on elucidating the mechanisms leading to and controlling PCD in response to adverse conditions in plants. This knowledge may help develop novel strategies to obtain more resilient crop varieties with improved tolerance and enhanced productivity. The aim of the present review is to summarize the recent advances in research on ROS-induced PCD related to abiotic stress and the role of the organelles in the process.
Supernova remnants (SNRs) are among the most important targets for gamma-ray observatories. Being prominent non-thermal sources, they are very likely responsible for the acceleration of the bulk of Galactic cosmic rays (CRS). To firmly establish the SNR paradigm for the origin of cosmic rays, it should be confirmed that protons are indeed accelerated in, and released from, SNRs with the appropriate flux and spectrum. This can be done by detailed theoretical models which account for microphysics of acceleration and various radiation processes of hadrons and leptons. The current generation of Cherenkov telescopes has insufficient sensitivity to constrain theoretical models. A new facility, the Cherenkov Telescope Array (CTA), will have superior capabilities and may finally resolve this long standing issue of high-energy astrophysics. We want to assess the capabilities of CTA to reveal the physics of various types of SNRs in the initial 2000 years of their evolution. During this time, the efficiency to accelerate cosmic rays is highest. We perform time-dependent simulations of the hydrodynamics, the magnetic fields, the cosmic-ray acceleration, and the non-thermal emission for type Ia, Ic and IIP SNRs. We calculate the CTA response to the y-ray emission from these SNRs for various ages and distances, and we perform a realistic analysis of the simulated data. We derive distance limits for the detectability and resolvability of these SNR types at several ages. We test the ability of CTA to reconstruct their morphological and spectral parameters as a function of their distance. Finally, we estimate how well CTA data will constrain the theoretical models. (C) 2014 Elsevier B.V. All rights reserved.
The biosynthesis of the molybdenum cofactors (Moco) is an ancient, ubiquitous, and highly conserved pathway leading to the biochemical activation of molybdenum. Moco is the essential component of a group of redox enzymes, which are diverse in terms of their phylogenetic distribution and their architectures, both at the overall level and in their catalytic geometry. A wide variety of transformations are catalyzed by these enzymes at carbon, sulfur and nitrogen atoms, which include the transfer of an oxo group or two electrons to or from the substrate. More than 50 molybdoenzymes were identified to date. In all molybdoenzymes except nitrogenase, molybdenum is coordinated to a dithiolene group on the 6-alkyl side chain of a pterin called molybdopterin (MPT). The biosynthesis of Moco can be divided into three general steps, with a fourth one present only in bacteria and archaea: (1) formation of the cyclic pyranopterin monophosphate, (2) formation of MPT, (3) insertion of molybdenum into molybdopterin to form Moco, and (4) additional modification of Moco in bacteria with the attachment of a nucleotide to the phosphate group of MPT, forming the dinucleotide variant of Moco. This review will focus on the biosynthesis of Moco in bacteria, humans and plants.
Ionogels (IGs), also termed ion gels, are functional hybrid materials based on an ionic liquid (IL) and a polymeric, hybrid, or inorganic matrix. IGs combine the properties of the matrix such as mechanical strength with IL properties like high ionic conductivity, high thermal stability, or catalytic activity. IGs are thus attractive for many applications, but the vast majority of IGs made and published so far are bulk materials or dense films. Applications like sensing or catalysis, however, would benefit from IGs with high surface areas or defined surface morphologies or architectures. In spite of this, only relatively few examples of high-surface-area IGs have been made so far; this has mostly been achieved by electrospinning, which has proven to be a promising strategy towards advanced IGs. The current review discusses first developments and outlines the future potential of electrospun ionogels, predominantly from a materials and inorganic chemistry perspective.
All components of the endothelin (ET) system are present in renal tubular cells. In this review, we summarize current knowledge about ET and the most common tubular diseases: acute kidney injury (AKI) and polycystic kidney disease. AKI originally was called acute tubular necrosis, pointing to the most prominent morphologic findings. Similarly, cysts in polycystic kidney disease, and especially in autosomal-dominant polycystic kidney disease, are of tubular origin. Preclinical studies have indicated that the ET system and particularly ETA receptors are involved in the pathogenesis of ischemia-reperfusion injury, although these findings have not been translated to clinical studies. The ET system also has been implicated in radiocontrast-dye-induced AKI, however, ET-receptor blockade in a large human study was not successful. The ET system is activated in sepsis models of AKI; the effectiveness of ET blocking agents in preclinical studies is variable depending on the model and the ET-receptor antagonist used. Numerous studies have shown that the ET system plays an important role in the complex pathophysiology associated with cyst formation and disease progression in polycystic kidney disease. However, results from selective targeting of ET-receptor subtypes in animal models of polycystic kidney disease have proved disappointing and do not support clinical trials. These studies have shown that a critical balance between ETA and ETB receptor action is necessary to maintain structure and function in the cystic kidney. In summary, ETs have been implicated in the pathogenesis of several renal tubulointerstitial diseases, however, experimental animal findings have not yet led to use of ET blockers in human beings. (C) 2015 Elsevier Inc. All rights reserved.
For a long time, the analysis of ancient human DNA represented one of the most controversial disciplines in an already controversial field of research. Scepticism in this field was only matched by the long-lasting controversy over the authenticity of ancient pathogen DNA. This ambiguous view on ancient human DNA had a dichotomous root. On the one hand, the interest in ancient human DNA is great because such studies touch on the history and evolution of our own species. On the other hand, because these studies are dealing with samples from our own species, results are easily compromised by contamination of the experiments with modern human DNA, which is ubiquitous in the environment. Consequently, some of the most disputed studies published - apart maybe from early reports on million year old dinosaur or amber DNA - reported DNA analyses from human subfossil remains. However, the development of so-called next-or second-generation sequencing (SGS) in 2005 and the technological advances associated with it have generated new confidence in the genetic study of ancient human remains. The ability to sequence shorter DNA fragments than with PCR amplification coupled to traditional Sanger sequencing, along with very high sequencing throughput have both reduced the risk of sequencing modern contamination and provided tools to evaluate the authenticity of DNA sequence data. The field is now rapidly developing, providing unprecedented insights into the evolution of our own species and past human population dynamics as well as the evolution and history of human pathogens and epidemics. Here, we review how recent technological improvements have rapidly transformed ancient human DNA research from a highly controversial subject to a central component of modern anthropological research. We also discuss potential future directions of ancient human DNA research.
Background Balance training (BT) has been used for the promotion of balance and sports-related skills as well as for prevention and rehabilitation of lower extremity sport injuries. However, evidence-based dose-response relationships in BT parameters have not yet been established.
Objective The objective of this systematic literature review and meta-analysis was to determine dose-response relationships in BT parameters that lead to improvements in balance in young healthy adults with different training status.
Data Sources A computerized systematic literature search was performed in the electronic databases PubMed, Web of Knowledge, and SPORTDiscus from January 1984 up to May 2014 to capture all articles related to BT in young healthy adults.
Study Eligibility Criteria A systematic approach was used to evaluate the 596 articles identified for initial review. Only randomized controlled studies were included if they investigated BT in young healthy adults (16-40 years) and tested at least one behavioral balance performance outcome. In total, 25 studies met the inclusion criteria for review.
Study Appraisal and Synthesis Methods Studies were evaluated using the physiotherapy evidence database (PEDro) scale. Within-subject effect sizes (ESdw) and between-subject effect sizes (ESdb) were calculated. The included studies were coded for the following criteria: training status (elite athletes, sub-elite athletes, recreational athletes, untrained subjects), training modalities (training period, frequency, volume, etc.), and balance outcome (test for the assessment of steady-state, proactive, and reactive balance).
Results Mean ESdb demonstrated that BT is an effective means to improve steady-state (ESdb = 0.73) and proactive balance (ESdb = 0.92) in healthy young adults. Studies including elite athletes showed the largest effects (ESdb = 1.29) on measures of steady-state balance as compared with studies analyzing sub-elite athletes (ESdb = 0.32), recreational athletes (ESdb = 0.69), and untrained subjects (ESdb = 0.82). Our analyses regarding dose-response relationships in BT revealed that a training period of 11-12 weeks (ESdb = 1.09), a training frequency of three (mean ESdb = 0.72) or six (single ESdb = 1.84) sessions per week, at least 16-19 training sessions in total (ESdb = 1.12), a duration of 11-15 min for a single training session (ESdb = 1.11), four exercises per training session (ESdb = 1.29), two sets per exercise (ESdb = 1.63), and a duration of 21-40 s for a single BT exercise (ESdb = 1.06) is most effective in improving measures of steady-state balance. Due to a small number of studies, dose-response relationships of BT for measures of proactive and reactive balance could not be qualified.
Limitations The present findings must be interpreted with caution because it is difficult to separate the impact of a single training modality (e.g., training frequency) from that of the others. Moreover, the quality of the included studies was rather limited, with a mean PEDro score of 5.
Conclusions Our detailed analyses revealed effective BT parameters for the improvement of steady-state balance. Thus, practitioners and coaches are advised to consult the identified dose-response relationships of this systematic literature review and meta-analysis to implement effective BT protocols in clinical and sports-related contexts. However, further research of high methodological quality is needed to (1) determine dose-response relationships of BT for measures of proactive and reactive balance, (2) define effective sequencing protocols in BT (e.g., BT before or after a regular training session), (3) discern the effects of detraining, and (4) develop a feasible and effective method to regulate training intensity in BT.
Framing Citizen Participation: Participatory Budgeting in France, Germany and the United Kingdom
(2015)
Continuing advances in 'omics methodologies and instrumentation is enhancing the understanding of how plants cope with the dynamic nature of their growing environment. 'Omics platforms have been only recently extended to cover horticultural crop species. Many of the most widely cultivated vegetable crops belong to the genus Brassica: these include plants grown for their root (turnip, rutabaga/swede), their swollen stem base (kohlrabi), their leaves (cabbage, kale, pak choi) and their inflorescence (cauliflower, broccoli). Characterization at the genome, transcript, protein and metabolite levels has illustrated the complexity of the cellular response to a whole series of environmental stresses, including nutrient deficiency, pathogen attack, heavy metal toxicity, cold acclimation, and excessive and sub optimal irradiation. This review covers recent applications of omics technologies to the brassicaceous vegetables, and discusses future scenarios in achieving improvements in crop end-use quality.