New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The DUNE far detector vertical drift technology. Technical design report

DUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

Potencial alelopático da parte aérea de Senna occidentalis (L.) Link (Fabaceae, Caesalpinioideae): bioensaios em laboratório

A bioatividade das frações semipurificadas (hexânica, acetato de etila e etanol-água) do extrato etanólico das partes aérea de S. occidentalis foi avaliada através de ensaios de germinação e de crescimento de Lactuca sativa (alface), Lycopersicon esculentum (tomate), Allium cepa (cebola) e Triticum aestivum (trigo), em laboratório. Foram utilizadas três concentrações (250, 500, 1000 mg L-1) de cada fração e um controle não tratado, com quatro repetições de 50 sementes. Os bioensaios de germinação revelaram que todas as frações atrasaram a germinação de alface, tomate e cebola, e as frações hexânica e acetato de etila reduziram a germinabilidade de tomate e cebola. Nos bioensaios de crescimento, a fração hexânica estimulou o crescimento da raiz e inibiu o crescimento do hipocótilo das eudicotiledôneas. A mesma fração inibiu o crescimento da raiz e do coleóptilo das monocotiledôneas. A fração acetato de etila inibiu o crescimento da raiz das plântulas-alvo e o hipocótilo/coleóptilo de tomate e cebola. A fração etanol-água estimulou o crescimento da raiz de tomate e do hipocótilo de alface e inibiu o crescimento da raiz de cebola e trigo e, também, do coleóptilo de cebola, na concentração de 1000 mg L-1. Nos bioensaios com herbicidas comerciais foram observados efeitos semelhantes àqueles obtidos na germinação pelas frações e no crescimento pelas frações hexânica e acetato de etila. Na cromatografia em camada delgada, foram detectados terpenos na fração hexânica, compostos fenólicos e alcalóides na fração acetato de etila. A análise espectrofotométrica revelou que a fração acetato de etila possui o maior conteúdo de compostos fenólicos e flavonóides.The bioactivity of semipurified fractions (hexane, ethyl acetate and ethanol-water) obtained from S. occidentalis aerial-part ethanol extract was evaluated by germination and growth bioassays using Lactuca sativa (lettuce), Lycopersicon esculentum (tomato), Allium cepa (onion) and Triticum aestivum (wheat), in the laboratory. Three concentrations of each fraction (250, 500, 1000 mg L-1) and untreated control were used, on four replicates of 50 seeds each. Germination bioassays revealed that lettuce, tomato and onion germination were delayed by all tested semipurified fractions, and tomato and onion germination were inhibited by the hexane and ethyl acetate fractions. In growth bioassays, the hexane fraction stimulated root growth and inhibited hypocotyl growth in the eudicots. The same fraction inhibited root and coleoptile growth of the assayed monocots. The ethyl acetate fraction inhibited seedling roots and hypocotyl/coleoptile growth, of tomato and onion. The ethanol-water fraction stimulated tomato root growth and lettuce hypocotyl growth, and inhibited onion and wheat root and onion coleoptile development at 1000 mg L-1. Bioassays performed with commercial herbicides presented similar results to those observed in germination to the semipurified fractions in the growth by hexane and ethyl acetate fractions. The layer chromatography revealed that the tested hexane fraction contains terpenes, and the ethyl acetate fraction has phenolic compounds and alkaloids. The spectrophotometric analysis revealed greater yields of phenolic compounds and flavonoids in the ethyl acetate fraction

Megalanthine, a Bioactive Sesquiterpenoid from Heliotropium megalanthum, its Degradation Products and their Bioactivities

The new bioactive sesquiterpenoid (3R,6E)-2,6,10-trimethyl-3-(3-p-hydroxyphenylpropanoyloxy)-dodeca-6,11-diene-2,10-diol, named megalanthine, was isolated from the resinous exudates of Heliotropium megalanthum. The degradation products of this compound were identified. Several plant-defensive properties (insecticidal, antifungal, and phytotoxic) were evaluated after obtaining positive results in a preliminary etiolated wheat coleoptile bioassay. This bioassay showed the need to have both the phenolic and sesquiterpene moieties of the natural product present to achieve a biological effect. This result was confirmed in phytotoxicity bioassays. Megalanthine was ruled out as a significant plant-plant defense agent because of its lack of stability. The positive results recorded in the antifungal and antifeedant tests suggest, however, that this chemical is relevant in several ecological interactions involving H. megalanthum

Upland Rice and Allelopathy

Upland rice (Oryza sativa L.) is mainly grown in Asia, Africa and Latin America. Yield potential of upland rice is quite low and invariably this crop is subjected to many environmental stresses. Further, when upland rice is grown in monoculture for more than two to three years on the same land, allelopathy or autotoxicity is frequently reported. Allelopathy involves complex plant and plant chemical interactions. The level of phytotoxicity of allelochemicals is influenced by abiotic and biotic soil factors. Adopting suitable management strategies in crop rotation can reduce or eliminate allelochemicals phytotoxicity. Rice yields can be improved by growing rice in rotation with other crop species. Allelochemicals of rice can be used for control of weeds in this crop as well as other crops that are grown in rotation with rice. This review highlights that present knowledge of allelopathy in upland rice is inadequate and fragmentary, and therefore, more controlled and field studies are needed to understand and to reduce the detrimental effects of allelopathy in the upland rice production