Evidence of suppression of onchocerciasis transmission in the Venezuelan Amazonian focus.

BACKGROUND: The World Health Organization (WHO) has set goals for onchocerciasis elimination in Latin America by 2015. Most of the six previously endemic countries are attaining this goal by implementing twice a year (and in some foci, quarterly) mass ivermectin (Mectizan®) distribution. Elimination of transmission has been verified in Colombia, Ecuador and Mexico. Challenges remain in the Amazonian focus straddling Venezuela and Brazil, where the disease affects the hard-to-reach Yanomami indigenous population. We provide evidence of suppression of Onchocerca volvulus transmission by Simulium guianense s.l. in 16 previously hyperendemic Yanomami communities in southern Venezuela after 15 years of 6-monthly and 5 years of 3-monthly mass ivermectin treatment. METHODS: Baseline and monitoring and evaluation parasitological, ophthalmological, entomological and serological surveys were conducted in selected sentinel and extra-sentinel communities of the focus throughout the implementation of the programme. RESULTS: From 2010 to 2012–2015, clinico-parasitological surveys indicate a substantial decrease in skin microfilarial prevalence and intensity of infection; accompanied by no evidence (or very low prevalence and intensity) of ocular microfilariae in the examined population. Of a total of 51,341 S. guianense flies tested by PCR none had L3 infection (heads only). Prevalence of infective flies and seasonal transmission potentials in 2012–2013 were, respectively, under 1 % and 20 L3/person/transmission season. Serology in children aged 1–10 years demonstrated that although 26 out of 396 (7 %) individuals still had Ov-16 antibodies, only 4/218 (2 %) seropositives were aged 1–5 years. CONCLUSIONS: We report evidence of recent transmission and morbidity suppression in some communities of the focus representing 75 % of the Yanomami population and 70 % of all known communities. We conclude that onchocerciasis transmission could be feasibly interrupted in the Venezuelan Amazonian focus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1313-z) contains supplementary material, which is available to authorized users

DNA-based Self-Assembly of Chiral Plasmonic Nanostructures with Tailored Optical Response

Surface plasmon resonances generated in metallic nanostructures can be utilized to tailor electromagnetic fields. The precise spatial arrangement of such structures can result in surprising optical properties that are not found in any naturally occurring material. Here, the designed activity emerges from collective effects of singular components equipped with limited individual functionality. Top-down fabrication of plasmonic materials with a predesigned optical response in the visible range by conventional lithographic methods has remained challenging due to their limited resolution, the complexity of scaling, and the difficulty to extend these techniques to three-dimensional architectures. Molecular self-assembly provides an alternative route to create such materials which is not bound by the above limitations. We demonstrate how the DNA origami method can be used to produce plasmonic materials with a tailored optical response at visible wavelengths. Harnessing the assembly power of 3D DNA origami, we arranged metal nanoparticles with a spatial accuracy of 2 nm into nanoscale helices. The helical structures assemble in solution in a massively parallel fashion and with near quantitative yields. As a designed optical response, we generated giant circular dichroism and optical rotary dispersion in the visible range that originates from the collective plasmon-plasmon interactions within the nanohelices. We also show that the optical response can be tuned through the visible spectrum by changing the composition of the metal nanoparticles. The observed effects are independent of the direction of the incident light and can be switched by design between left- and right-handed orientation. Our work demonstrates the production of complex bulk materials from precisely designed nanoscopic assemblies and highlights the potential of DNA self-assembly for the fabrication of plasmonic nanostructures.Comment: 5 pages, 4 figure

The Dimroth rearrangement as a probable cause for structural misassignments in imidazo[1,2-a]pyrimidines: A 15N-labelling study and an easy method for the determination of regiochemistry

Structural misassignments are often seen for complex natural products, but this can also be an issue with seemingly simpler structures. In this paper, we describe how, using a15N-labelled analogue, we established that the Dimroth rearrangement can occur in imidazo[1,2-a]pyrimidines and result in an incorrect regiochemical assignment of such compounds. These studies supported a rearrangement mechanism involving addition of hydroxide ion followed by ring opening. It was also observed that C(2) and C(3) substituted regioisomers could be readily distinguished using1H NMR spectroscopy

Chiral plasmonics of self-assembled nanorod dimers

Chiral nanoscale photonic systems typically follow either tetrahedral or helical geometries that require four or more different constituent nanoparticles. Smaller number of particles and different chiral geometries taking advantage of the self-organization capabilities of nanomaterials will advance understanding of chiral plasmonic effects, facilitate development of their theory, and stimulate practical applications of chiroplasmonics. Here we show that gold nanorods self-assemble into side-by-side orientated pairs and ‘‘ladders’’ in which chiral properties originate from the small dihedral angle between them. Spontaneous twisting of one nanorod versus the other one breaks the centrosymmetric nature of the parallel assemblies. Two possible enantiomeric conformations with positive and negative dihedral angles were obtained with different assembly triggers. The chiral nature of the angled nanorod pairs was confirmed by 4p full space simulations and the first example of single-particle CD spectroscopy. Self-assembled nanorod pairs and ‘‘ladders’’ enable the development of chiral metamaterials, (bio)sensors, and new catalytic processes

Plasma and cerebrospinal fluid glial fibrillary acidic protein levels in adults with Down syndrome: a longitudinal cohort study

Background: The diagnosis of symptomatic Alzheimer's disease is a clinical challenge in adults with Down syndrome. Blood biomarkers would be of particular clinical importance in this population. The astrocytic Glial Fibrillary Acidic Protein (GFAP) is a marker of astrogliosis associated with amyloid pathology, but its longitudinal changes, association with other biomarkers and cognitive performance have not been studied in individuals with Down syndrome. Methods: We performed a three-centre study of adults with Down syndrome, autosomal dominant Alzheimer's disease and euploid individuals enrolled in Hospital Sant Pau, Barcelona (Spain), Hospital Clinic, Barcelona (Spain) and Ludwig-Maximilians-Universität, Munich (Germany). Cerebrospinal fluid (CSF) and plasma GFAP concentrations were quantified using Simoa. A subset of participants had PET 18F-fluorodeoxyglucose, amyloid tracers and MRI measurements. Findings: This study included 997 individuals, 585 participants with Down syndrome, 61 Familial Alzheimer's disease mutation carriers and 351 euploid individuals along the Alzheimer's disease continuum, recruited between November 2008 and May 2022. Participants with Down syndrome were clinically classified at baseline as asymptomatic, prodromal Alzheimer's disease and Alzheimer's disease dementia. Plasma GFAP levels were significantly increased in prodromal and Alzheimer's disease dementia compared to asymptomatic individuals and increased in parallel to CSF Aβ changes, ten years prior to amyloid PET positivity. Plasma GFAP presented the highest diagnostic performance to discriminate symptomatic from asymptomatic groups (AUC = 0.93, 95% CI 0.9−0.95) and its concentrations were significantly higher in progressors vs non-progressors (p < 0.001), showing an increase of 19.8% (11.8–33.0) per year in participants with dementia. Finally, plasma GFAP levels were highly correlated with cortical thinning and brain amyloid pathology. Interpretation: Our findings support the utility of plasma GFAP as a biomarker of Alzheimer's disease in adults with Down syndrome, with possible applications in clinical practice and clinical trials. Funding: AC Immune, La Caixa Foundation, Instituto de Salud Carlos III, National Institute on Aging, Wellcome Trust, Jérôme Lejeune Foundation, Medical Research Council, Alzheimer's Association, National Institute for Health Research, EU Joint Programme–Neurodegenerative Disease Research, Alzheimer's Society, Deutsche Forschungsgemeinschaft, Stiftung für die Erforschung von Verhaltens, Fundación Tatiana Pérez de Guzmán el Bueno & European Union's Horizon 2020 und Umwelteinflüssen auf die menschliche Gesundheit

Effects of Global Warming on Ancient Mammalian Communities and Their Environments

Current global warming affects the composition and dynamics of mammalian communities and can increase extinction risk; however, long-term effects of warming on mammals are less understood. Dietary reconstructions inferred from stable isotopes of fossil herbivorous mammalian tooth enamel document environmental and climatic changes in ancient ecosystems, including C(3)/C(4) transitions and relative seasonality.Here, we use stable carbon and oxygen isotopes preserved in fossil teeth to document the magnitude of mammalian dietary shifts and ancient floral change during geologically documented glacial and interglacial periods during the Pliocene (approximately 1.9 million years ago) and Pleistocene (approximately 1.3 million years ago) in Florida. Stable isotope data demonstrate increased aridity, increased C(4) grass consumption, inter-faunal dietary partitioning, increased isotopic niche breadth of mixed feeders, niche partitioning of phylogenetically similar taxa, and differences in relative seasonality with warming.Our data show that global warming resulted in dramatic vegetation and dietary changes even at lower latitudes (approximately 28 degrees N). Our results also question the use of models that predict the long term decline and extinction of species based on the assumption that niches are conserved over time. These findings have immediate relevance to clarifying possible biotic responses to current global warming in modern ecosystems

Antibiotics Threaten Wildlife: Circulating Quinolone Residues and Disease in Avian Scavengers

Antibiotic residues that may be present in carcasses of medicated livestock could pass to and greatly reduce scavenger wildlife populations. We surveyed residues of the quinolones enrofloxacin and its metabolite ciprofloxacin and other antibiotics (amoxicillin and oxytetracycline) in nestling griffon Gyps fulvus, cinereous Aegypius monachus and Egyptian Neophron percnopterus vultures in central Spain. We found high concentrations of antibiotics in the plasma of many nestling cinereous (57%) and Egyptian (40%) vultures. Enrofloxacin and ciprofloxacin were also found in liver samples of all dead cinereous vultures. This is the first report of antibiotic residues in wildlife. We also provide evidence of a direct association between antibiotic residues, primarily quinolones, and severe disease due to bacterial and fungal pathogens. Our results indicate that, by damaging the liver and kidney and through the acquisition and proliferation of pathogens associated with the depletion of lymphoid organs, continuous exposure to antibiotics could increase mortality rates, at least in cinereous vultures. If antibiotics ingested with livestock carrion are clearly implicated in the decline of the vultures in central Spain then it should be considered a primary concern for conservation of their populations

Association between the rs6950982 polymorphism near the SERPINE1 gene and blood pressure and lipid parameters in a high-cardiovascular-risk population: interaction with Mediterranean diet

The SERPINE1 (serpin peptidase inhibitor, clade E, member 1) gene, better known by its previous symbol PAI-1 (plasminogen activator inhibitor 1), has been associated with cardiovascular phenotypes with differing results. Our aim was to examine the association between the rs6950982 (G > A) near the SERPINE1 gene, blood pressure (BP) and plasma lipid concentrations as well as the modulation of the polymorphism effects by adherence to Mediterranean diet (AMD). We studied 945 high-cardiovascular-risk subjects. Biochemical, clinical, dietary and genetic data (rs6950982) were obtained. We also determined the common rs1799768 (4G/5G), for checking independent effects. AMD was measured by a validated questionnaire, and four groups were considered. rs6950982 (A > G) and rs1799768 (4G/5G) were only in moderate–low linkage disequilibrium (D′ = 0.719; r2 = 0.167). The most significant associations we obtained were with rs6950982 (A > G). In males, the G allele was nominally associated with higher diastolic BP (AA: 81.5 ± 10.9, AG: 82.1 ± 11.4, GG: 85.7 ± 10.5 mmHg; Padditive = 0.030) and systolic BP (AA + AG: 141.4 ± 6.9 mmHg vs. GG: 149.8 ± 8.0 mmHg; Precessive = 0.036). In the whole population, the rs6950982 was also associated with plasma lipids. Subject with the G allele presented higher total cholesterol (Padditive = 0.016, Precessive = 0.011), low-density lipoprotein cholesterol (Padditive = 0.032, Precessive = 0.031) and triglycerides (Padditive = 0.040, Precessive = 0.029). AMD modulated the effect of rs6950982 on triglyceride concentrations (P for interaction = 0.036). Greater AMD reduced the higher triglyceride concentrations in GG subjects. No significant interactions were found for the other parameters. The rs6950982 was associated with higher BP in men and higher triglycerides in the whole population, this association being modulated by AMD

Reversed flow of Atlantic deep water during the Last Glacial Maximum

The meridional overturning circulation (MOC) of the Atlantic Ocean is considered to be one of the most important components of the climate system. This is because its warm surface currents, such as the Gulf Stream, redistribute huge amounts of energy from tropical to high latitudes and influence regional weather and climate patterns, whereas its lower limb ventilates the deep ocean and affects the storage of carbon in the abyss, away from the atmosphere. Despite its significance for future climate, the operation of the MOC under contrasting climates of the past remains controversial. Nutrient-based proxies1, 2 and recent model simulations3 indicate that during the Last Glacial Maximum the convective activity in the North Atlantic Ocean was much weaker than at present. In contrast, rate-sensitive radiogenic 231Pa/230Th isotope ratios from the North Atlantic have been interpreted to indicate only minor changes in MOC strength4, 5, 6. Here we show that the basin-scale abyssal circulation of the Atlantic Ocean was probably reversed during the Last Glacial Maximum and was dominated by northward water flow from the Southern Ocean. These conclusions are based on new high-resolution data from the South Atlantic Ocean that establish the basin-scale north to south gradient in 231Pa/230Th, and thus the direction of the deep ocean circulation. Our findings are consistent with nutrient-based proxies and argue that further analysis of 231Pa/230Th outside the North Atlantic basin will enhance our understanding of past ocean circulation, provided that spatial gradients are carefully considered. This broader perspective suggests that the modern pattern of the Atlantic MOC—with a prominent southerly flow of deep waters originating in the North Atlantic—arose only during the Holocene epoch