RNA-based vaccines against SARS-CoV-2 have proven critical to limiting COVID-19 disease severity and spread. Cellular mechanisms driving antigen-specific responses to these vaccines, however, remain ...uncertain. Here we identify and characterize antigen-specific cells and antibody responses to the RNA vaccine BNT162b2 using multiple single-cell technologies for in depth analysis of longitudinal samples from a cohort of healthy participants. Mass cytometry and unbiased machine learning pinpoint an expanding, population of antigen-specific memory CD4
and CD8
T cells with characteristics of follicular or peripheral helper cells. B cell receptor sequencing suggest progression from IgM, with apparent cross-reactivity to endemic coronaviruses, to SARS-CoV-2-specific IgA and IgG memory B cells and plasmablasts. Responding lymphocyte populations correlate with eventual SARS-CoV-2 IgG, and a participant lacking these cell populations failed to sustain SARS-CoV-2-specific antibodies and experienced breakthrough infection. These integrated proteomic and genomic platforms identify an antigen-specific cellular basis of RNA vaccine-based immunity.
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable ...challenge to the clinical treatment of coronavirus disease (COVID-19). Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the linking B cell receptor to antigen specificity through sequencing (LIBRA-seq) technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 shows potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryoelectron microscopy (cryo-EM) structure of 54042-4 in complex with the SARS-CoV-2 spike reveals an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses uncommon genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings provide motivation for the development of 54042-4 as a lead candidate to counteract current and future SARS-CoV-2 VOCs.
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•LIBRA-seq identifies 54042-4, a potently neutralizing SARS-CoV-2 antibody•54042-4 maintains potent neutralization against Alpha, Beta, Gamma, and Delta VOCs•The epitope of 54042-4 is highly conserved among current SARS-CoV-2 isolates
Kramer et al. demonstrate that antibody 54042-4 recognizes residues highly conserved across global SARS-CoV-2 isolates. Antibody 54042-4 potently neutralizes all known circulating variants of concern (VOCs) and could be developed as a clinical candidate to treat COVID-19 infection.
Intensidade da ramulose sob semeadura convencional e direta do algodoeiro Salvatierra, Daniela Kubiak de(Universidade de São Paulo Escola Superior de Agricultura Luiz de Queiroz Universidade Federal de Mato Grosso do Sul,CAPES); Chiavegato, Ederaldo José(Universidade de São Paulo Escola Superior de Agricultura Luiz de Queiroz Departamento de Produção Vegetal); Silva, Ariana Vieira e(Universidade de São Paulo Escola Superior de Agricultura Luiz de Queiroz Departamento de Produção Vegetal,CAPES)
Bragantia,
2009, 20090001, Letnik:
68, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Foram realizados em Piracicaba (SP), em 2004/05 e 2005/06, experimentos com o algodoeiro (Gossypium hirsutum L. var. latifolium Hutch), sob preparo do solo e semeadura convencional; e ausência de ...preparo do solo com semeadura sobre palhada de milheto, com o objetivo de avaliar as modificações microclimáticas (temperatura e duração do período de molhamento-DPM), decorrentes da utilização da palhada de milheto, no desenvolvimento da ramulose (Colletotrichum gossypii South. var. cephalosporioides Costa) do algodoeiro. Foi utilizado também um índice de favorabilidade temperatura-molhamento (IF-tm) para a ramulose do algodoeiro, para avaliar o desenvolvimento da doença nos dois sistemas de semeadura. Os dados climáticos foram medidos por uma plataforma de aquisição de dados sob o dossel das plantas e na região central da área experimental. A ramulose foi avaliada por escala de notas (1 a 5) e as médias das notas analisadas estatisticamente. Alterações no progresso da doença foram observadas, com ocorrência mais severa no sistema convencional de semeadura, porém não podendo ser atribuídas às variações na temperatura e DPM, consideradas isoladamente, mas decorrente de interações entre estas e a precipitação pluvial. O IF-tm teve boa relação com o aumento da severidade da doença, e a diferença, observada em maior proporção no sistema convencional de semeadura, ocorreu em períodos cujos valores de IF-tm foram altos, associados a períodos com chuvas e fase de maior suscetibilidade das plantas ao patógeno. Com IF-tm menores que 0,500 não se observa aumento efetivo da severidade da ramulose em quaisquer sistema de semeadura.
During the years of 2004/05 and 2005/06, in Piracicaba, State of São Paulo, experiments were carried out with cotton crop under conventional tillage seeding and no-tillage. The seeding was performed over the mulching of millet, with the objective to evaluate if such mulching could interfere on temperature, leaf wetness duration (LWD) and development of ramulosis in cotton crop. It was also used the Favorability Index for the based on ramulosis cotton crop to explain the development differences of the disease the two seeding systems. Weather variables data were measured by an of acquisition data platform of the experimental area. The disease was measured by scales from 1 to 5 and the average was submitted to a statistic analysis. The difference on ramulosis severity between cotton crop under conventional tillage and conventional seeding was due to specific interactions for each period where many variables were involved (stage of the development of the plant and the macro and microclimatic conditions). The favorability index had a good relation with the increase of the ramulosis severity between both seeding systems. Ramulosis severity can be higher in conventional production system than in systems that uses mulching, particularly in periods when the index values are high: association of rain periods with crop susceptibility to the pathogen. When the index is lower than 0,500 effective increases on ramulosis severity is not observed in any seeding system.
Background Endometrial cancer (EC) mortality is particularly high among non-Hispanic Blacks and is twice that of non-Hispanic Whites. However, comparisons of EC survival outcomes by race/ethnicity ...are often confounded by histology and grade. Here, we analyze EC survival disparities in multiracial Florida with a focus on EC types (1 and 2) and subtypes, defined according to histology and grade. Methods All 27,809 cases of EC diagnosed during 2005–2016 were obtained from the Florida Cancer Registry. Age-standardized, 5-year cause-specific survival by race/ethnicity and histological type were calculated. Fine and Gray competing risk regression was used to estimate sub-distribution hazard ratios (sHRs) for associations between risk of death due to EC and potential predictive factors such as histology/grade, age, stage at diagnosis, and insurance. Results Type 2 EC accounted for only 38.7% of all incident EC-cases but 74.6% of all EC-deaths. Blacks were disproportionately affected by type 2 EC (57.6%) compared to Whites, Hispanics, and Asians (35.6%, 37.7%, and 43.0%, respectively). Age-adjusted 5-year survival for types 1 and 2 were 85.3% and 51.6%, respectively; however, there was wide variation within type 2 subtypes, ranging from 60.2% for mixed cell EC to as low as 30.1% for carcinosarcoma. In the multivariable model, Blacks with type 2 EC had a 23% higher risk of death due to EC (sHR: 1.23, 95%CI: 1.12–1.36) compared to Whites. Conclusions Population-based analyses should consider the histological heterogeneity of EC because the less common type 2 EC drives racial/ethnic survival disparities in EC. Black women have a higher proportion of more aggressive histological types and an overall higher risk of death due to EC than Whites. To the extent that some of these histological types may be considered different diseases and require specific treatment approaches, further research on etiology and prognosis for detailed type 2 EC subtypes is warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Temporal variation of temperature-health associations depends on the combination of two pathways: pure adaptation to increasingly warmer temperatures due to climate change, and other attenuation ...mechanisms due to non-climate factors such as infrastructural changes and improved health care. Disentangling these pathways is critical for assessing climate change impacts and for planning public health and climate policies. We present evidence on this topic by assessing temporal trends in cold- and heat-attributable mortality risks in a multi-country investigation.
Trends in country-specific attributable mortality fractions (AFs) for cold and heat (defined as below/above minimum mortality temperature, respectively) in 305 locations within 10 countries (1985–2012) were estimated using a two-stage time-series design with time-varying distributed lag non-linear models. To separate the contribution of pure adaptation to increasing temperatures and active changes in susceptibility (non-climate driven mechanisms) to heat and cold, we compared observed yearly-AFs with those predicted in two counterfactual scenarios: trends driven by either (1) changes in exposure-response function (assuming a constant temperature distribution), (2) or changes in temperature distribution (assuming constant exposure-response relationships). This comparison provides insights about the potential mechanisms and pace of adaptation in each population.
Heat-related AFs decreased in all countries (ranging from 0.45–1.66% to 0.15–0.93%, in the first and last 5-year periods, respectively) except in Australia, Ireland and UK. Different patterns were found for cold (where AFs ranged from 5.57–15.43% to 2.16–8.91%), showing either decreasing (Brazil, Japan, Spain, Australia and Ireland), increasing (USA), or stable trends (Canada, South Korea and UK). Heat-AF trends were mostly driven by changes in exposure-response associations due to modified susceptibility to temperature, whereas no clear patterns were observed for cold.
Our findings suggest a decrease in heat-mortality impacts over the past decades, well beyond those expected from a pure adaptation to changes in temperature due to the observed warming. This indicates that there is scope for the development of public health strategies to mitigate heat-related climate change impacts. In contrast, no clear conclusions were found for cold. Further investigations should focus on identification of factors defining these changes in susceptibility.
•Evidence on adaptation is crucial for the assessment of climate change impacts.•Most of the studied countries showed a strong reduction in heat vulnerability.•We found more diffuse patterns on cold-mortality trends.•Pace of decrease in heat susceptibility was faster than the observed warming.•There is scope for development of mitigation strategies of climate change impacts.
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•Acidic conditions favored O&G removal from emulsions using cork granules.•O&G sorption onto cork granules is governed by a partition mechanism.•Ionic strength plays an important role ...in oil sorption at near neutral pH values.•O&G sorption onto cork granules is negatively affected by surfactants.•The effect of surfactants on O&G sorption is minimized by electrolytes.
The present work focuses on the use of two different cork by-products, raw cork (RAC) and regranulated cork (RGC), as sorbents for oil and grease (O&G) removal from mineral oil-in-water (O/W) emulsions (lubricant oil 15W-40). Acidic conditions favored O&G removal from emulsions using cork granules, achieving values of about 90%. RGC showed the highest O&G removal capacity, associated with its thermal treatment with water vapor at 380°C, which increased its hydrophobicity. Sorption isotherms at 25°C were determined at different pH values (2, 4 and 6). Freundlich and linear models were able to fit well the equilibrium data regarding O&G removal using RGC, suggesting that the major sorption mechanism is partitioning (log KOW around 4.0). Kinetic studies showed that O&G removal rates using RGC were faster (<100min) than those using RAC (≈300min). Moreover, oil sorption onto cork is favored by acidic conditions, achieving values of 90mgg−1 at pH 2 (equilibrium oil concentration in the liquid phase of 4.5mg/L). In order to improve the oil uptake onto regranulated cork at near neutral pH, the use of different salts (NaCl, Na2SO4 and MgCl2) and surfactants (anionic: sodium dodecyl sulfate – SDS, cationic: hexadecyltrimethyl ammonium – HDTMA and nonionic: Tween 80) was tested. The best results were achieved using 0.1M NaCl and Tween 80. This paper also proposes a mass transfer model based on cork and oil properties, which adequately predicts the kinetic experimental data and attests that the rate-limiting step in the sorption process is the external fluid film resistance.
Few studies have examined variation in the associations between heat waves and mortality in an international context.
We aimed to systematically examine the impacts of heat waves on mortality with ...lag effects internationally.
We collected daily data of temperature and mortality from 400 communities in 18 countries/regions and defined 12 types of heat waves by combining community-specific daily mean temperature ≥90th, 92.5th, 95th, and 97.5th percentiles of temperature with duration ≥2, 3, and 4 d. We used time-series analyses to estimate the community-specific heat wave-mortality relation over lags of 0-10 d. Then, we applied meta-analysis to pool heat wave effects at the country level for cumulative and lag effects for each type of heat wave definition.
Heat waves of all definitions had significant cumulative associations with mortality in all countries, but varied by community. The higher the temperature threshold used to define heat waves, the higher heat wave associations on mortality. However, heat wave duration did not modify the impacts. The association between heat waves and mortality appeared acutely and lasted for 3 and 4 d. Heat waves had higher associations with mortality in moderate cold and moderate hot areas than cold and hot areas. There were no added effects of heat waves on mortality in all countries/regions, except for Brazil, Moldova, and Taiwan. Heat waves defined by daily mean and maximum temperatures produced similar heat wave-mortality associations, but not daily minimum temperature.
Results indicate that high temperatures create a substantial health burden, and effects of high temperatures over consecutive days are similar to what would be experienced if high temperature days occurred independently. People living in moderate cold and moderate hot areas are more sensitive to heat waves than those living in cold and hot areas. Daily mean and maximum temperatures had similar ability to define heat waves rather than minimum temperature. https://doi.org/10.1289/EHP1026.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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