Control of the Light Interaction in a Semiconductor Nanoparticle Dimer Through Scattering Directionality

11 págs.; 4 figs.; 1 tab.Dimers of nanoparticles are very interesting for several devices due to the possibility of obtaining intense light concentrations in the gap between them. A dynamic control of this interaction to obtain either the maximum or minimum light through interferential effects could be also relevant for a multitude of devices such as chemical sensors or all-optical devices for interchip/intrachip communications. Semiconductor nanoparticles satisfying Kerker conditions present an anisotropic scattering distribution with a minimum in either the forward or the backward direction and prominent scattering in the contrary direction. The reduction or enhancement of the electromagnetic field in a certain direction can minimize or maximize the interaction with neighboring nanoparticles. In this paper, we consider a dimer of nanoparticles such that each component satisfies each one of the Kerker conditions. Depending on the arrangement of the nanoparticles with respect to the impinging light direction, we can produce a minimum or a maximum of the electric field between them, reducing or maximizing the interferential effects. The strong dependence of the directional conditions with external conditions, such as the incident wavelength, can be used to dynamically control the light concentration in the gap. Ó 2016 IEEEThis work was supported in part by the Ministerio de Economía y Competitividad of Spain under Grant TEC2013—50138—EXP and Grant TEC2013-47342-C2-2-R, by the RD Program of the Comunidad de Madrid under Grant SINFOTON S2013/MIT—2790, and by COST Action IC1208.Peer Reviewe

Sildenafil restores cognitive function without affecting β-amyloid burden in a mouse model of Alzheimer's disease

Abstract BACKGROUND AND PURPOSE: Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory-related behaviour were investigated. EXPERIMENTAL APPROACH: Sildenafil was administered to the Tg2576 transgenic mouse model of Alzheimer's disease and to age-matched negative littermates (controls). Memory function was analysed using the Morris water maze test and fear conditioning tasks. Biochemical analyses were performed in brain lysates from animals treated with saline or with sildenafil. KEY RESULTS: Treatment of aged Tg2576 animals with sildenafil completely reversed their cognitive impairment. Such changes were accompanied in the hippocampus by a reduction of tau hyperphosphorylation and a decrease in the activity of glycogen synthase kinase 3β (GSK3β) and of cyclin-dependent kinase 5 (CDK5) (p25/p35 ratio). Moreover, sildenafil also increased levels of brain-derived neurotrophic factor (BDNF) and the activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus without any detectable modification of brain amyloid burden. CONCLUSIONS AND IMPLICATIONS: Sildenafil improved cognitive functions in Tg2576 mice and the effect was not related to changes in the amyloid burden. These data further strengthen the potential of sildenafil as a therapeutic agent for Alzheimer's disease

PLA2 G4E, a candidate gene for resilience in Alzheimer's disease and a new target for dementia treatment

Clinical studies revealed that some aged-individuals accumulate a significant number of histopathological Alzheimer´s disease (AD) lesions in their brain, yet without developing any signs of dementia. Animal models of AD represent suitable tools to identify genes that might promote cognitive resilience and hence, this study first set out to identify cognitively resilient individuals in the aged-Tg2576 mouse model. A transcriptomic analysis of these mice identified PLA2 G4E as a gene that might confer resistance to dementia. Indeed, a significant decrease in PLA2 G4E is evident in the brain of late-stage AD patients, whereas no such changes are observed in early stage patients with AD neuropathological lesions but no signs of dementia. We demonstrated that adeno-associated viral vector-mediated overexpression of PLA2 G4E in hippocampal neurons completely restored cognitive deficits in elderly APP/PS1 mice, without affecting the amyloid or tau pathology. These PLA2 G4E overexpressing APP/PS1 mice developed significantly more dendritic spines than sham-injected mice, coinciding with the cognitive improvement observed. Hence, these results support the idea that a loss of PLA2 G4E might play a key role in the onset of dementia in AD, highlighting the potential of PLA2 G4E overexpression as a novel therapeutic strategy to manage AD and other disorders that course with memory deficits

16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index

Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology

Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARγ) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated. Here, in mice overexpressing mutant human amyloid precursor protein, we found that chronic treatment with rosiglitazone, a high-affinity agonist at PPARγ, facilitated β-amyloid peptide (Aβ) clearance. Rosiglitazone not only reduced Aβ burden in the brain but, importantly, almost completely removed the abundant amyloid plaques observed in the hippocampus and entorhinal cortex of 13-month-old transgenic mice. In the hippocampus, neuropil threads containing phosphorylated tau, probably corresponding to dystrophic neurites, were also decreased by the drug. Rosiglitazone switched on the activated microglial phenotype, promoting its phagocytic ability, reducing the expression of proinflammatory markers and inducing factors for alternative differentiation. The decreased amyloid pathology may account for the reduction of p-tau-containing neuropil threads and for the rescue of impaired recognition and spatial memory in the transgenic mice. This study provides further insights into the mechanisms for the beneficial effect of rosiglitazone in AD patients

The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM

The activation of ATR-ATRIP in response to double-stranded DNA breaks (DSBs) depends upon ATM in human cells and Xenopus egg extracts. One important aspect of this dependency involves regulation of TopBP1 by ATM. In Xenopus egg extracts, ATM associates with TopBP1 and thereupon phosphorylates it on S1131. This phosphorylation enhances the capacity of TopBP1 to activate the ATR-ATRIP complex. We show that TopBP1 also interacts with the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. This interaction involves the Nbs1 subunit of the complex. ATM can no longer interact with TopBP1 in Nbs1-depleted egg extracts, which suggests that the MRN complex helps to bridge ATM and TopBP1 together. The association between TopBP1 and Nbs1 involves the first pair of BRCT repeats in TopBP1. In addition, the two tandem BRCT repeats of Nbs1 are required for this binding. Functional studies with mutated forms of TopBP1 and Nbs1 suggested that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. These findings suggest that the MRN complex is a crucial mediator in the process whereby ATM promotes the TopBP1-dependent activation of ATR-ATRIP in response to DSBs

Immunomodulatory properties of carvone inhalation and Its effects on contextual fear memory in mice

A complex network of interactions exists between the immune, the olfactory, and the central nervous system (CNS). Inhalation of different fragrances can affect immunological reactions in response to an antigen but also may have effects on the CNS and cognitive activity. We performed an exploratory study of the immunomodulatory ability of a series of compounds representing each of the 10 odor categories or clusters described previously. We evaluated the impact of each particular odor on the immune response after immunization with the model antigen ovalbumin in combination with the TLR3 agonist poly I:C. We found that some odors behave as immunostimulatory agents, whereas others might be considered as potential immunosuppressant odors. Interestingly, the immunomodulatory capacity was, in some cases, strain-specific. In particular, one of the fragrances, carvone, was found to be immunostimulatory in BALB/c mice and immunosuppressive in C57BL/6J mice, facilitating or impairing viral clearance, respectively, in a model of a viral infection with a recombinant adenovirus. Importantly, inhalation of the odor improved the memory capacity in BALB/c mice in a fear-conditioning test, while it impaired this same capacity in C57BL/6J mice. The improvement in memory capacity in BALB/c was associated with higher CD3+ T cell infiltration into the hippocampus and increased local expression of mRNA coding for IL-1β, TNF-α, and IL-6 cytokines. In contrast, the memory impairment in C57BL/6 was associated with a reduction in CD3 numbers and an increase in IFN-γ. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals. These results highlight the potential of studying odors as therapeutic agents for CNS-related diseases

Infratrochlear neuralgia: A prospective series of seven patients treated with infratrochlear nerve blocks

BACKGROUND: Infratrochlear neuralgia is a recently described painful cranial neuropathy that causes pain in the internal angle of the orbit and the medial upper eyelid, the upper bridge of the nose and/or the lacrimal caruncle. We aim to present seven new cases of infratrochlear neuralgia treated with anaesthetic nerve blocks. METHODS: Over an 18-month period, we prospectively identified seven cases of infratrochlear neuralgia among the patients attending the Headache Unit in a tertiary hospital. Anaesthetic blocks were performed by injecting 0.5 cc of bupivacaine 0.5% at the emergence of the nerve above the internal canthus. RESULTS: All patients were women, and the mean age was 49.1 years (standard deviation, 17.9). The pain appeared at the internal angle of the orbit and/or the medial upper eyelid in six cases, and the whole territory of the infratrochlear nerve in one case. Six patients had continuous pain and one had episodes lasting 8–24 hours. All patients showed sensory disturbances within the painful area and tenderness upon palpation of the infratrochlear nerve. Nerve blocks resulted in complete and long-lasting relief in four patients and short-lasting relief in the other three patients. CONCLUSIONS: Infratrochlear neuralgia should be considered among the neuralgic causes of orbital and periorbital pain. Anaesthetic blocks may assist clinicians in the diagnosis and may also be an effective therapy