TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

Portuguese propolis disturbs glycolytic metabolism of human colorectal cancer in vitro

Propolis is a resin collected by bees from plant buds and exudates, which is further processed through the activity of bee enzymes. Propolis has been shown to possess many biological and pharmacological properties, such as antimicrobial, antioxidant, immunostimulant and antitumor activities. Due to this bioactivity profile, this resin can become an alternative, economic and safe source of natural bioactive compounds.Antitumor action has been reported in vitro and in vivo for propolis extracts or its isolated compounds; however, Portuguese propolis has been little explored. The aim of this work was to evaluate the in vitro antitumor activity of Portuguese propolis on the human colon carcinoma cell line HCT-15, assessing the effect of different fractions (hexane, chloroform and ethanol residual) of a propolis ethanol extract on cell viability, proliferation, metabolism and death. METHODS: Propolis from Angra do Heroísmo (Azores) was extracted with ethanol and sequentially fractionated in solvents with increasing polarity, n-hexane and chloroform. To assess cell viability, cell proliferation and cell death, Sulforhodamine B, BrDU incorporation assay and Anexin V/Propidium iodide were used, respectively. Glycolytic metabolism was estimated using specific kits. RESULTS: All propolis samples exhibited a cytotoxic effect against tumor cells, in a dose- and time-dependent way. Chloroform fraction, the most enriched in phenolic compounds, appears to be the most active, both in terms of inhibition of viability and cell death. Data also show that this cytotoxicity involves disturbance in tumor cell glycolytic metabolism, seen by a decrease in glucose consumption and lactate production. CONCLUSION: Our results show that Portuguese propolis from Angra do Heroísmo (Azores) can be a potential therapeutic agent against human colorectal cancer.We thank the Portuguese Science and Technology Foundation (FCT) for VMG fellowship (ref. SFRH/BI/33503/2008). The authors thank Mr. Antonio Marques from Frutercoop - Azores, who kindly collected and provided the propolis sample for the study

Antimicrobial activity and bioactive compounds of portuguese wild edible mushrooms methanolic extracts

The antimicrobial properties of phenolic extracts of Portuguese wild edible mushroom species (Lactarius deliciosus, Sarcodon imbricatus and Tricholoma portentosum) against pathogens were investigated. The minimal inhibitory concentrations (MICs) were evaluated for the entire mushroom, the cap and the stipe, separately; the portion of the mushroom used proved to be influenced in the results obtained, which are directly correlated with the content of total phenols and flavonoids in the extracts. The growth of Grampositive bacteria (Bacillus cereus, B. subtilis,) was well inhibited by these mushrooms, while Escherichia coli (Gramnegative bacteria) was resistant. The study on the antifungal effect of these mushrooms revealed that Candida albicans and Cryptococcus neoformans were differently inhibited for the mushrooms used

Modelling ranging behaviour of female orang-utans: a case study in Tuanan, Central Kalimantan, Indonesia

Quantification of the spatial needs of individuals and populations is vitally important for management and conservation. Geographic information systems (GIS) have recently become important analytical tools in wildlife biology, improving our ability to understand animal movement patterns, especially when very large data sets are collected. This study aims at combining the field of GIS with primatology to model and analyse space-use patterns of wild orang-utans. Home ranges of female orang-utans in the Tuanan Mawas forest reserve in Central Kalimantan, Indonesia were modelled with kernel density estimation methods. Kernel results were compared with minimum convex polygon estimates, and were found to perform better, because they were less sensitive to sample size and produced more reliable estimates. Furthermore, daily travel paths were calculated from 970 complete follow days. Annual ranges for the resident females were approximately 200 ha and remained stable over several years; total home range size was estimated to be 275 ha. On average, each female shared a third of her home range with each neighbouring female. Orang-utan females in Tuanan built their night nest on average 414 m away from the morning nest, whereas average daily travel path length was 777 m. A significant effect of fruit availability on day path length was found. Sexually active females covered longer distances per day and may also temporarily expand their ranges

Frequency of extreme Sahelian storms tripled since 1982 in satellite observations

The hydrological cycle is expected to intensify under global warming, with studies reporting more frequent extreme rain events in many regions of the world, and predicting increases in future flood frequency. Such early, predominantly mid-latitude observations are essential because of shortcomings within climate models in their depiction of convective rainfall. A globally important group of intense storms—mesoscale convective systems (MCSs)—poses a particular challenge, because they organize dynamically on spatial scales that cannot be resolved by conventional climate models. Here, we use 35 years of satellite observations from the West African Sahel to reveal a persistent increase in the frequency of the most intense MCSs. Sahelian storms are some of the most powerful on the planet, and rain gauges in this region have recorded a rise in ‘extreme’ daily rainfall totals. We find that intense MCS frequency is only weakly related to the multidecadal recovery of Sahel annual rainfall, but is highly correlated with global land temperatures. Analysis of trends across Africa reveals that MCS intensification is limited to a narrow band south of the Sahara desert. During this period, wet-season Sahelian temperatures have not risen, ruling out the possibility that rainfall has intensified in response to locally warmer conditions. On the other hand, the meridional temperature gradient spanning the Sahel has increased in recent decades, consistent with anthropogenic forcing driving enhanced Saharan warming. We argue that Saharan warming intensifies convection within Sahelian MCSs through increased wind shear and changes to the Saharan air layer. The meridional gradient is projected to strengthen throughout the twenty-first century, suggesting that the Sahel will experience particularly marked increases in extreme rain. The remarkably rapid intensification of Sahelian MCSs since the 1980s sheds new light on the response of organized tropical convection to global warming, and challenges conventional projections made by general circulation models

Evaluation of phenolic contents and antioxidant activity of various solvent extracts of Sonchus asper (L.) Hill

<p>Abstract</p> <p>Background</p> <p><it>Sonchus asper </it>(SA) is traditionally used for the treatment of various ailments associated with liver, lungs and kidneys. This study was aimed to investigate the therapeutic potential of nonpolar (hexane, SAHE; ethyl acetate, SAEE and chloroform, SACE) and polar (methanol, SAME) crude extracts of the whole plant.</p> <p>Methods</p> <p>To achieve these goals, several parameters including free-radical (DPPH^•, ABTS^•+, H₂O₂and ^•OH) scavenging, iron chelating activity, scavenging of superoxide radicals, total flavonoids and total phenolic content (TPC) were examined.</p> <p>Results</p> <p>The SA extracts presented a remarkable capacity to scavenge all the tested reactive species with IC₅₀values being found at the μg ⁄ ml level. The SAME was shown to have the highest TPCs while lowest IC₅₀values for the DPPH^•, ABTS^•+radical scavenging capacities and iron chelating scavenging efficiency, moreover, SAME had best activities in scavenging of superoxide radicals and hydrogen peroxide as well as potently scavenged the hydroxyl radicals.</p> <p>Conclusion</p> <p>These results suggest the potential of <it>S. asper </it>as a medicine against free-radical-associated oxidative damage.</p

Situação epidemiológica das meningites por haemophilus influenzae b na Direção Regional de Piracicaba - São Paulo

O presente estudo objetivou caracterizar a população acometida por meningites por Hib em relação às variáveis demográficas e relativas ao processo saúde-doença, no período de 1992 a 2001, na DIR de Piracicaba, SP, Brasil. Os dados foram coletados a partir de fichas de notificação compulsória, sendo sistematizados através do Programa SINAN. Observou-se que ocorreu um pico de incidência da doença em 1994, e um pico de óbitos em 1999, anteriores à introdução da vacina. Os mais acometidos foram crianças menores de 5 anos, do sexo masculino, confirmando dados de literatura. A maioria dos pacientes foi atendida em unidades hospitalares públicas de Piracicaba e Limeira, referências para as comunidades desses municípios, concretizando um dos princípios do Sistema Único de Saúde (SUS): a regionalização. A introdução da vacina promoveu redução dos casos em cerca de 73%, o que corrobora a sua importância e impele à necessidade de estimular a adesão à vacinação.El presente estudio objetivó caracterizar la población afectada por meningitis causada por Hib en relación a las variables demográficas y relativas al proceso salud-enfermedad, en el período de 1992 a 2001 en la DIR de Piracicaba, SP, Brasil. Los datos fueron recolectados a partir de fichas de notificación obligatorias, las cuales fueron sistematizadas a través del programa SINAN. Se observó que ocurrió un pico de incidencia de la enfermedad en 1994 y un pico de fallecimientos en 1999, con antelación a la introducción de la vacuna. Los más afectados fueron niños menores de 5 años, de sexo masculino, confirmando datos de la bibliografía. La mayoría de los pacientes fue atendida en unidades hospitalarias públicas de Piracicaba y Limeira, referenciales para las comunidades de tales municipios, concretando uno de los principios del Sistema Único de Salud (SUS): su regionalización. La introducción de la vacuna promovió la reducción de casos en cerca del 73%, lo que corrobora su importancia e impulsa la necesidad de estimular la adhesión a la vacunación.The objective of the present study was to characterize the population affected by Hib meningitis from 1992 to 2001, in the Regional Health Board of Piracicaba (São Paulo-Brazil) in terms of variables regarding demographics and the health-disease process. Data were collected from disease notification reports, and arranged using the SINAN Data Program . It was observed there was a peak in the incidence of meningitis in 1994 and a peak of deaths in 1999, before the vaccine had been introduced. The most affected group were male children under the age of 5 years, which is in agreement with literature. Most patients received care at public hospitals in the municipalities of Piracicaba and Limeira, which are references for the community of the entire region, which puts into effect one of the axes of the Health System of Brazil (SUS): regionalization. The introduction of the vaccine reduced incidence in about 73%, which corroborates its importance and shows that is necessary to encourage adherence to vaccination

Why male orangutans do not kill infants

Infanticide is widespread among mammals, is particularly common in primates, and has been shown to be an adaptive male strategy under certain conditions. Although no infanticides in wild orangutans have been reported to date, several authors have suggested that infanticide has been an important selection pressure influencing orangutan behavior and the evolution of orangutan social systems. In this paper, we critically assess this suggestion. We begin by investigating whether wild orangutans have been studied for a sufficiently long period that we might reasonably expect to have detected infanticide if it occurs. We consider whether orangutan females exhibit counterstrategies typically employed by other mammalian females. We also assess the hypothesis that orangutan females form special bonds with particular “protector males” to guard against infanticide. Lastly, we discuss socioecological reasons why orangutan males may not benefit from infanticide. We conclude that there is limited evidence for female counterstrategies and little support for the protector male hypothesis. Aspects of orangutan paternity certainty, lactational amenorrhea, and ranging behavior may explain why infanticide is not a strategy regularly employed by orangutan males on Sumatra or Borneo

Genome-Wide Association Studies of Cognitive and Motor Progression in Parkinson's Disease

BACKGROUND: There are currently no treatments that stop or slow the progression of Parkinson's disease (PD). Case-control genome-wide association studies have identified variants associated with disease risk, but not progression. The objective of the current study was to identify genetic variants associated with PD progression. METHODS: We analyzed 3 large longitudinal cohorts: Tracking Parkinson's, Oxford Discovery, and the Parkinson's Progression Markers Initiative. We included clinical data for 3364 patients with 12,144 observations (mean follow-up 4.2 years). We used a new method in PD, following a similar approach in Huntington's disease, in which we combined multiple assessments using a principal components analysis to derive scores for composite, motor, and cognitive progression. These scores were analyzed in linear regression in genome-wide association studies. We also performed a targeted analysis of the 90 PD risk loci from the latest case-control meta-analysis. RESULTS: There was no overlap between variants associated with PD risk, from case-control studies, and PD age at onset versus PD progression. The APOE ε4 tagging variant, rs429358, was significantly associated with composite and cognitive progression in PD. Conditional analysis revealed several independent signals in the APOE locus for cognitive progression. No single variants were associated with motor progression. However, in gene-based analysis, ATP8B2, a phospholipid transporter related to vesicle formation, was nominally associated with motor progression (P = 5.3 × 10-6 ). CONCLUSIONS: We provide early evidence that this new method in PD improves measurement of symptom progression. We show that the APOE ε4 allele drives progressive cognitive impairment in PD. Replication of this method and results in independent cohorts are needed. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society

Antioxidant activity of oils extracted from orange (Citrus sinensis) seeds

Due to the increasing production of food in the world with consequent increase of the production of waste, the importance of developing researches for its use is noticed. Thus, the interest in vegetable oils with bioactive compounds, such as the ones extracted from fruit seeds, is growing. Therefore, the present study aims to characterize the oils extracted from seeds of Hamlin, Natal, Pera-rio and Valencia orange varieties (Citrus sinensis), as to the levels of total carotenoids, total phenolic compounds, tocopherols and phytosterols, as well as to determine their antioxidant activity. The orange seed oils presented important content of total carotenoids (19.01 mg/kg), total phenolic compounds (4.43 g/kg), α-tocopherol (135.65 mg/kg) and phytosterols (1304.2 mg/kg). The antioxidant activity ranged from 56.0% (Natal) to 70.2% (Pera-rio). According to the results it is possible to conclude that the orange seed oils can be used as specialty oils in diet, since they contain considerable amounts of bioactive compounds and antioxidants