Perversions with a twist

PESS acknowledges grant FCT SFRH/BD/76369/201. MHG acknowledges PTDC/CTM-BIO/6178/2014.Perversions connecting two helices with symmetric handedness are a common occurrence in nature, for example in tendrils. These defects can be found in our day life decorating ribbon gifts or when plants use tendrils to attach to a support. Perversions arise when clamped elastic filaments coil into a helical shape but have to conserve zero overall twist. We investigate whether other types of perversions exist and if they display different properties. Here we show mathematically and experimentally that a continuous range of different perversions can exist and present different geometries. Experimentally, different perversions were generated using micro electrospun fibres. Our experimental results also confirm that these perversions behave differently upon release and adopt different final configurations. These results also demonstrate that it is possible to control on demand the formation and shape of microfilaments, in particular, of electrospun fibres by using ultraviolet light.publishersversionpublishe

Structural Color and Iridescence in Transparent Sheared Cellulosic Films

Shear transparent cellulose free-standing thin films can develop iridescence similar to that found in petals of the tulip Queen of the Night. The iridescence of the film arises from the modulation of the surface into bands periodically spread perpendicular to the shear direction. Small amounts of nanocrystalline cellulose (NCC) rods in the precursor liquid-crystalline solutions do not disturb the optical properties of the solutions but enhance the mechanical characteristics of the films and affects their iridescence. Smaller bands periodicity, not affected by the NCC rods, slightly deviated from the shear direction is also observed. NCCs are crucial to tune and understand the film's surface features formation. Our findings could lead to new materials for application in soft reflective screens and devices

Activation pathway to amino acid adducts

Funding: This work was supported in part by Fundação para a Ciência e a Tecnologia (FCT), Portugal (PTDC/QUI-QUI/113910/2009, RECI/QEQ-MED/0330/2012, UID/QUI/00100/2013 and IF/ 01091/2013/CP1163/CT0001), and by Interagency Agreement Y1ES1027 between the National Center for Toxicological Research/Food and Drug Administration and the National Institute of Environmental Health Sciences/National Toxicology Program. The opinions expressed in this paper do not necessarily represent those of the U.S. Food and Drug Administration. RW, ALG, ILM and SGH thank FCT for postdoctoral and doctoral fellowships (SFRH/BPD/70953/2010, SFRH/BD/72301/2010, SFRH/BD/75426/2010 and SFRH/BD/ 80690/2011, respectively). AMM also acknowledges Programa Operacional Potencial Humano from FCT and the European Social Fund (IF/01091/2013), and the LRI Innovative Science Award. We thank the Portuguese NMR and MS networks (IST nodes) for providing access to the facilities.Nevirapine (NVP) is the non-nucleoside HIV-1 reverse transcriptase inhibitor most commonly used in developing countries, both as a component of combined antiretroviral therapy and to prevent mother-to-child transmission of the virus; however, severe hepatotoxicity and serious adverse cutaneous effects raise concerns about its safety. NVP metabolism yields several phenolic derivatives conceivably capable of undergoing further metabolic oxidation to electrophilic quinoid derivatives prone to react with bionucleophiles and initiate toxic responses. We investigated the ability of two phenolic NVP metabolites, 2-hydroxy-NVP and 3-hydroxy-NVP, to undergo oxidation and subsequent reaction with bionucleophiles. Both metabolites yielded the same ring-contraction product upon oxidation with Frémy's salt in aqueous medium. This is consistent with the formation of a 2,3-NVP-quinone intermediate, which upon stabilization by reduction was fully characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. Additionally, we established that the oxidative activation of 2-hydroxy-NVP involved the transient formation of both the quinone and a quinone-imine, whereas 3-hydroxy-NVP was selectively converted into 2,3-NVP-quinone. The oxidations of 2-hydroxy-NVP and 3-hydroxy-NVP in the presence of the model amino acids ethyl valinate (to mimic the highly reactive N-terminal valine of hemoglobin) and N-acetylcysteine were also investigated. Ethyl valinate reacted with both 2,3-NVP-quinone and NVP-quinone-imine, yielding covalent adducts. By contrast, neither 2,3-NVP-quinone nor NVP-derived quinone-imine reacted with N-acetylcysteine. The product profile observed upon Frémy's salt oxidation of 2-hydroxy-NVP in the presence of ethyl valinate was replicated with myeloperoxidase-mediated oxidation. Additionally, tyrosinase-mediated oxidations selectively yielded 2,3-NVP-quinone-derived products, while quinone-imine-derived products were obtained upon lactoperoxidase catalysis. These observations suggest that the metabolic conversion of phenolic NVP metabolites into quinoid electrophiles is biologically plausible. Moreover, the lack of reaction with sulfhydryl groups might hamper the in vivo detoxification of NVP-derived quinone and quinone-imine metabolites via glutathione conjugation. As a result, these metabolites could be available for reaction with nitrogen-based bionucleophiles (e.g., lysine residues of proteins) ultimately eliciting toxic events.publishersversionpublishe

CHARACTERIZATION OF THE LITTERFALL PRODUCTION AND SEED RAIN IN A RESERVE OF SEASONAL SEMIDECIDUOUS FOREST, PARAN\uc1 STATE

O objetivo do estudo foi analisar a produ\ue7\ue3o de serapilheira e a chuva de sementes em um fragmento de Floresta Estacional Semidecidual do oeste do Paran\ue1 com 242 ha, que \ue9 conhecido como Reserva Particular de Patrim\uf4nio Natural Fazenda Santa Maria. O material foi coletado mensalmente de junho/2011 a maio/2012, em nove parcelas de 20 x 20 m, com o uso quatro coletores de 0,5 x 0,5 m em cada parcela. A serapilheira foi triada e pesada, e a chuva de sementes foi avaliada quanto \ue0 riqueza, forma de vida, categoria sucessional e s\uedndrome de dispers\ue3o das esp\ue9cies encontradas. A produ\ue7\ue3o anual de serapilheira foi de 11.886 kg ha-1, sendo agosto e setembro os meses de maiores produ\ue7\uf5es. A fra\ue7\ue3o foliar foi a mais representativa com 58,52% do total. Na chuva de sementes foram coletadas 18.300 sementes, distribu\ueddas em 79 morfoesp\ue9cies, das quais 51 foram identificadas em n\uedvel de esp\ue9cie, oito em n\uedvel de g\ueanero e seis em n\uedvel de fam\uedlia. Mikania sp., Cecropia pachystachya , Pisonia aculeata , Gouania ulmifolia e Dendropanax cuneatus foram as esp\ue9cies com maiores densidades relativas. Os meses com maior abund\ue2ncia de sementes foram setembro (19%), outubro (20%), novembro (27%) e mar\ue7o (15%). A forma de vida predominante foi arb\uf3rea com 76,27% das esp\ue9cies, seguida de lianas com 20,34% e herb\ue1ceas com apenas 3,39%. Entre as esp\ue9cies arb\uf3reas, 37% foram representadas pela categoria sucessional de pioneiras, enquanto as categorias secund\ue1rias iniciais e tardias representaram 22% cada e as clim\ue1cicas 20%. A zoocoria predominou entre as s\uedndromes de dispers\ue3o (52,54%), enquanto a anemocoria e a autocoria ocorreram em 38,98 e 8,47%, respectivamente. Os resultados foram semelhantes aos encontrados em outros trabalhos realizados em Florestas Estacionais Semideciduais tardias. Assim, por meio deste estudo sobre deposi\ue7\ue3o da serapilheira e chuva de sementes, o fragmento florestal pode ser considerado uma \ue1rea de floresta tardia e com elevado potencial de regenera\ue7\ue3o.This study aimed to analyze litterfall production and seed rain of a fragment of seasonal semideciduous forest from western of Parana state with 242 ha, which is known as Santa Maria Farm\u2019s Private Nature Reserve. The material was collected from June/2011 to May/2012, in nine plots of 20 x 20 m, using four traps of 0,5 x 0,5 m in each plot. The litter was sorted and weighed, and the seed rain was evaluated as the wealth, life form, successional category and dispersal syndrome of the species found. The annual litterfall production was 11.886 kg ha-1, being August and September the months of the largest production. The leaf fraction was the most representative with 58,52% of the total. In the seed rain were collected 18.300 seeds, distributed in 79 morphospecies, which 51 were identified to species level, eight at the genus level and six at the family level. Mikania sp., Cecropia pachystachya , Pisonia aculeata , Gouania ulmifolia and Dendropanax cuneatus , were the species with the highest relative densities. The months with the highest abundance of seeds were September (19%), October (20%), November (27%) and March (15%). The life form predominant was tree with 76,27% of the species, followed by climbers with 20,34% and herbaceous with 3,39% only. Among the tree species, 37 % were represented by successional category of pioneer, while the early and late secondary categories accounted for 22% each and the climax 20%. The zoochory predominated among dispersal syndromes (52,54%), while anemochory and autocory occurred in 38,98% and 8,47%, respectively. The results were similar to those found in other works performed in late seasonal semideciduous forest. Furthermore, through this study about litterfall production and seed rain, the forest fragment can be considered an area of mature forest and with high regeneration potential

REHABILITATION OF A DEGRADED AREA IN THE FIELD OF SEMIDECIDUOUS SEASONAL FOREST UNDER DIFFERENT TREATMENTS

Objetivou-se avaliar tr\ueas tratamentos de restaura\ue7\ue3o florestal em uma \ue1rea com eleva\ue7\ue3o peri\uf3dica do len\ue7ol fre\ue1tico, no Corredor de Biodiversidade Santa Maria, localizado entre os munic\uedpios de Santa Terezinha de Itaipu e S\ue3o Miguel do Igua\ue7u-PR. Os tratamentos foram: controle, aduba\ue7\ue3o verde e solariza\ue7\ue3o do solo. Foi realizado o acompanhamento mensal da mortalidade e desenvolvimento de 12 esp\ue9cies arb\uf3reas nativas da regi\ue3o e a persist\ueancia de duas esp\ue9cies invasoras presentes na \ue1rea, Megathyrsus maximus (capim-coloni\ue3o) e Cyperus rotundus (tiririca). Al\ue9m disso, avaliou-se as altera\ue7\uf5es promovidas no solo por meio de tr\ueas coletas durante o experimento. Ap\uf3s um ano, os tratamentos n\ue3o apresentaram diferen\ue7as estat\uedsticas significativas sobre as avalia\ue7\uf5es realizadas. A mortalidade foi mais acentuada em janeiro (12,08%), com maior percentual para Cabralea canjerana (canjarana) e menor para Luehea divaricata (a\ue7oita-cavalo). Sobre o desenvolvimento das mudas, houve maior crescimento para: Sapium glandulatum (leiteiro-do-banhado), Croton urucurana (sangra-d\u2019\ue1gua) e Luehea divaricata, com acr\ue9scimos mensais em di\ue2metro de 3,66 mm a 4,12mm, e em altura de 12,39 cm a 17,02 cm. Em rela\ue7\ue3o \ue0 massa seca do capimcoloni\ue3o e tiririca em todos os tratamentos, os maiores valores foram verificados em janeiro (94,14 g m-2) e fevereiro (132,76 g m-2), mantendo-se baixos ao longo do experimento. Por meio das an\ue1lises de solo, foi poss\uedvel observar que os tratamentos n\ue3o apresentaram diferen\ue7as significativas, contudo, as altera\ue7\uf5es f\uedsicas e qu\uedmicas do solo mostraram-se sens\uedveis ao manejo das esp\ue9cies invasoras, podendo levar a novas modifica\ue7\uf5es durante o desenvolvimento das mudas.It was aimed to evaluate three treatments for forest restoration in an area with periodic elevation of the groundwater, in the Corredor de Biodiversidade Santa Maria, located between the cities of Santa Teresinha de Itaipu and S\ue3o Miguel do Igua\ue7u, in Paran\ue1 state. The treatments were: control, green manure and soil solarization. It was performed a monthly monitoring of mortality and development of 12 tree native species of the region and the persistence of two invasive species present in the area, Megathyrsus maximus (coloniao grass) and Cyperus rotundus (coco grass). Furthermore, it was evaluated the changes introduced in the soil by three soil samples during the experiment. After over a year of assessment, the treatments showed no statistically significant differences on the evaluations. The mortality was more pronounced in January (12.08%), with a higher percentage for Cabralea canjerana (canjarana) and lower for Luehea divaricata (a\ue7oita-cavalo). About the seedlings development, growth was higher for: Sapium glandulatum (leiteiro-do-banhado), Croton urucurana (sangra-d\u2019\ue1gua) and Luehea divaricata, with monthly increases in diameter of 3.66 mm to 4.12 mm, and height of 12.39 cm to 17.02 cm. Regarding the dry mass of \u2018coloni\ue3o\u2019 grass and coco grass (nutsedge) in all treatments, the highest values were found in January (94.14 g m-2) and February (132.76 g m-2), remaining low throughout the experiment. Through soil analyzes, it was observed that treatments showed no significant differences, however, the physical and chemical changes in the soil were sensitive to the invasive species management, which may lead to new modifications during the growth of seedlings

Neutrophil elastase promotes Leishmania donovani infection via interferon-β

Visceral leishmaniasis is a deadly illness caused by Leishmania donovani that provokes liver and spleen inflammation and tissue destruction. In cutaneous leishmaniasis, the protein of L. major named inhibitor of serine peptidases (ISP2) inactivates neutrophil elastase (NE) present at the macrophage surface, resulting in blockade of TLR4 activation, prevention of TNF and IFN production and parasite survival. We report poor intracellular growth of L. donovani in macrophages from knock-out mice for NE (ela-/-), TLR4 or TLR2. NE and TLR4 co-localized with the parasite in the parasitophorous vacuole. Parasite load in the liver and spleen of ela-/- mice were reduced and accompanied by increased nitric oxide and decreased TGF production. Expression of ISP2 was not detected in L. donovani and a transgenic line constitutively expressing ISP2, displayed poor intracellular growth in macrophages and decreased burden in mice. Infected ela-/- macrophages displayed significantly lower IFN mRNA than background mice macrophages and the intracellular growth of was fully restored by exogenous IFN. We propose that L. donovani utilizes the host NE-TLR machinery to induce IFN necessary for parasite survival/growth during early infection. Low or absent expression of parasite ISP2 in L. donovani is necessary to preserve the activation of the NE-TLR pathway

Estimating how inflated or obscured effects of climate affect forecasted species distribution

Climate is one of the main drivers of species distribution. However, as different environmental factors tend to co-vary, the effect of climate cannot be taken at face value, as it may be either inflated or obscured by other correlated factors. We used the favourability models of four species (Alytes dickhilleni, Vipera latasti, Aquila fasciata and Capra pyrenaica) inhabiting Spanish mountains as case studies to evaluate the relative contribution of climate in their forecasted favourability by using variation partitioning and weighting the effect of climate in relation to non-climatic factors. By calculating the pure effect of the climatic factor, the pure effects of non-climatic factors, the shared climatic effect and the proportion of the pure effect of the climatic factor in relation to its apparent effect (r), we assessed the apparent effect and the pure independent effect of climate. We then projected both types of effects when modelling the future favourability for each species and combination of AOGCM-SRES (two Atmosphere-Ocean General Circulation Models: CGCM2 and ECHAM4, and two Special Reports on Emission Scenarios (SRES): A2 and B2). The results show that the apparent effect of climate can be either inflated (overrated) or obscured (underrated) by other correlated factors. These differences were species-specific; the sum of favourable areas forecasted according to the pure climatic effect differed from that forecasted according to the apparent climatic effect by about 61% on average for one of the species analyzed, and by about 20% on average for each of the other species. The pure effect of future climate on species distributions can only be estimated by combining climate with other factors. Transferring the pure climatic effect and the apparent climatic effect to the future delimits the maximum and minimum favourable areas forecasted for each species in each climate change scenario.Ministerio de Ciencia e Innovación and FEDER (project CGL2009-11316/BOS). D. Romero is a PhD student at the University of Malaga with a grant of the Ministerio de Educacio´n y Ciencia (AP 2007-03633

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens