Colloidal nanoparticles as advanced biological sensors

Biological sensing using nanoparticles Colloidal fluorescent and plasmonic nanoparticles yield intense responses to incident light, making them useful as sensors or probes for sensitive detection in solution. Howes et al. review the potential uses of nanoparticle biosensors in research and diagnostics. A range of methods allow for the chemical modification of the particle surfaces so that they can be tuned for specific analytes and give optical signals for a range of biological conditions of interest. Signals can be detected in complex media or in vivo making the particles of interest for both laboratory research and in clinical settings. Science , this issue 10.1126/science.1247390 </jats:p

A review of Laser Powder Bed Fusion Additive Manufacturing of aluminium alloys: Microstructure and properties

Additive manufacturing (AM) of metallic alloys for structural and functional applications has attracted significant interest in the last two decades as it brings a step change in the philosophy of design and manufacturing. The ability to design and fabricate complex geometries not amenable to conventional manufacturing, and the potential to reduce component weight without compromising performance, is particularly attractive for aerospace and automotive applications. This has culminated in rapid progress in AM with Ti- and Ni-based alloys. In contrast, the development of AM with Al-alloys has been slow, despite their widespread adoption in industry owing to an excellent combination of low density and high strength-to-weight ratio. Research to date has focused on castable and weldable AlSiMg-based alloys (which are less desirable for demanding structural applications), as well as on the development of new AM-specific AlMgSc alloys (based on 5xxx series). However, high strength wrought Al-alloys have typically been unsuitable for AM due to their unfavourable microstructural characteristics under rapid directional solidification conditions. Nevertheless, recent research has shown that there is promise in overcoming the associated challenges. Herein, we present a review of the current status of AM with Al-alloys. We primarily focus on the microstructural characteristics, and on exploring how these influence mechanical properties. The current metallurgical understanding of microstructure and defect formation in Al-alloys during AM is discussed, along with recent promising research exploring various microstructural modification methodologies. Finally, the remaining challenges in the development of AM with high-strength Al-alloys are discussed

Emerging pharmacotherapy for cancer patients with cognitive dysfunction

Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient's mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer's drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction

How nanotechnology-enabled concepts could contribute to the prevention, diagnosis and therapy of bacterial infections

This viewpoint summarizes a selection of nanotechnology-based key concepts relevant to critical care medicine. It focuses on novel approaches for a trigger-dependent release of antimicrobial substances from degradable nano-sized carriers, the ultra-sensitive detection of analytes in body fluid samples by plasmonic and fluorescent nanoparticles, and the rapid removal of pathogens from whole blood using magnetic nanoparticles. The concepts presented here could significantly contribute to the prevention, diagnosis and therapy of bacterial infections in future and it is now our turn to bring them from the bench to the bedside

Molecular imaging in schizophrenia spectrum disorders

In this chapter, we aim to shed light on the schizophrenia spectrum disorders using molecular imaging. Schizophrenia spectrum disorders consist primarily of the disorders with full-blown psychosis in their course and are grouped in the DSM-V category of schizophrenia and other psychotic disorders. The treatment of psychosis has been very successful in the era of psychopharmacology, starting with the discovery of the "neuroleptic" drug chlorpromazine (Largactil). The notion that the so-called typical antipsychotics bind to dopamine D2 and D3 receptors is one of the cornerstones of the dopamine hypothesis of schizophrenia (Davis et al., Am J Psychiatry 148:1474-1486, 1991). For more than a decade, this hypothesis has been the most influential hypothesis in schizophrenia research. It postulates that schizophrenia is a manifestation of a "hyperdopaminergic" state in some regions of the brain. The binding of antipsychotics to D2/D3 receptors can be directly visualized and quantified with dopamine receptor PET and SPECT ligands, such as [11C]-raclopride or [123I]-IBZM, respectively (Laruelle, Q J Nucl Med 42:211-221, 1998). Typical antipsychotics bind to D2/D3 receptors and displace these radiotracers from the postsynaptic receptors in the dopamine projection areas, such as the striatum, providing a unique way to quantify occupancy of these compounds to the D2/D3 receptors. In one of the first human studies with [11C]-raclopride, described that an occupancy of 70-80% of the D2/D3 receptors was sufficient for its antipsychotic effects while parkinsonistic effects were associated with much higher occupancies. The anti-dopaminergic effects in the striatum explain the major side effect of typical antipsychotics, i.e., parkinsonism. Very efficacious second-line or "atypical" antipsychotics appear to be less dependent on D2 blockade for clinical effect. The major example of this line of drugs is clozapine. Clozapine acts partly by its affinity for the postsynaptic 5HT2A receptor but has "pleiotropic" effects by affecting many other neurotransmitter receptors, hormone receptors, and inflammatory mediators. However, it was found that the newer "atypical" antipsychotics marketed after clozapine still bind for a large proportion to dopamine D2/D3 receptors, which contributes significantly to their antipsychotic efficacy. Despite the enormous progress in the development of antipsychotics, and growth of choice for the clinician to treat schizophrenia, the effect remains limited to a suppressive effect on the positive psychotic symptoms, like delusions and hallucinations. Antipsychotics do not cure the disease and have major metabolic side effects, like weight gain, increasing the risk for diabetes enormously. Therefore, more knowledge on the working mechanism and the discovery of alternative molecular pathways of treatment are needed. It is the aim of this chapter to translate molecular imaging in experimental models of schizophrenia and patients to better understand the etiopathogenesis of the clinical syndrome of schizophrenia. The ultimate aim is to design better prevention, care, and cure for schizophrenia by pinpointing to the molecular focus of the disease process.</p

Population Structure and Gene Flow of the Yellow Anaconda (Eunectes notaeus) in Northern Argentina

Yellow anacondas (Eunectes notaeus) are large, semiaquatic boid snakes found in wetland systems in South America. These snakes are commercially harvested under a sustainable management plan in Argentina, so information regarding population structuring can be helpful for determination of management units. We evaluated genetic structure and migration using partial sequences from the mitochondrial control region and mitochondrial genes cyt-b and ND4 for 183 samples collected within northern Argentina. A group of landscape features and environmental variables including several treatments of temperature and precipitation were explored as potential drivers of observed genetic patterns. We found significant population structure between most putative population comparisons and bidirectional but asymmetric migration in several cases. The configuration of rivers and wetlands was found to be significantly associated with yellow anaconda population structure (IBD), and important for gene flow, although genetic distances were not significantly correlated with the environmental variables used here. More in-depth analyses of environmental data may be needed to fully understand the importance of environmental conditions on population structure and migration. These analyses indicate that our putative populations are demographically distinct and should be treated as such in Argentina's management plan for the harvesting of yellow anacondas

Wavelength-scale errors in optical localization due to spin-orbit coupling of light

The precise determination of the position of point-like emitters and scatterers using far-field optical imaging techniques is of utmost importance for a wide range of applications in medicine, biology, astronomy, and physics. Although the optical wavelength sets a fundamental limit to the image resolution of unknown objects, the position of an individual emitter can in principle be estimated from the image with arbitrary precision. This is used, e.g., in stars' position determination and in optical super-resolution microscopy. Furthermore, precise position determination is an experimental prerequisite for the manipulation and measurement of individual quantum systems, such as atoms, ions, and solid state-based quantum emitters. Here we demonstrate that spin-orbit coupling of light in the emission of elliptically polarized emitters can lead to systematic, wavelength-scale errors in the estimate of the emitter's position. Imaging a single trapped atom as well as a single sub-wavelength-diameter gold nanoparticle, we demonstrate a shift between the emitters' measured and actual positions which is comparable to the optical wavelength. Remarkably, for certain settings, the expected shift can become arbitrarily large. Beyond their relevance for optical imaging techniques, our findings apply to the localization of objects using any type of wave that carries orbital angular momentum relative to the emitter's position with a component orthogonal to the direction of observation.Comment: Main text 6 pages, Methods 8 pages, Extended data 9 pages, Supplementary information 4 page

Advancing schizophrenia drug discovery : optimizing rodent models to bridge the translational gap

Although our knowledge of the pathophysiology of schizophrenia has increased, treatments for this devastating illness remain inadequate. Here, we critically assess rodent models and behavioural end points used in schizophrenia drug discovery and discuss why these have not led to improved treatments. We provide a perspective on how new models, based on recent advances in the understanding of the genetics and neural circuitry underlying schizophrenia, can bridge the translational gap and lead to the development of more effective drugs. We conclude that previous serendipitous approaches should be replaced with rational strategies for drug discovery in integrated preclinical and clinical programmes. Validation of drug targets in disease-based models that are integrated with translationally relevant end point assessments will reduce the current attrition rate in schizophrenia drug discovery and ultimately lead to therapies that tackle the disease process