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The interface between climate and ecosystem structure and function is incompletely understood, partly because few ecological records start before the recent warming phase. Here, we analyse an exceptional 100-yr long record of the great tit (Parus major) population in Switzerland in relation to climate and habitat phenology. Using structural equation analysis, we demonstrate an uninterrupted cascade of significant influences of the large-scale atmospheric circulation (North-Atlantic Oscillation, NAO, and North-sea - Caspian Pattern, NCP) on habitat and breeding phenology, and further on fitness-relevant life history traits within great tit populations. We then apply the relationships of this analysis to reconstruct the circulation-driven component of fluctuations in great tit breeding phenology and productivity on the basis of new seasonal NAO and NCP indices back to 1500 AD. According to the structural equation model, the multi-decadal oscillation of the atmospheric circulation likely led to substantial variation in habitat phenology, productivity and consequently, tit population fluctuations with minima during the “Maunder Minimum” (～ 1650-1720) and the Little Ice Age Type Event I (1810-1850). The warming since 1975 was not only related with a quick shift towards earlier breeding, but also with the highest productivity since 1500, and thus, the impact of the NAO and NCP has contributed to an unprecedented increase of the population. A verification of the structural equation model against two independent data series (1970-2000 and 1750-1900) corroborates that the retrospective model reliably depicts the major long-term NAO/NCP impact on ecosystem parameters. The results suggest a complex cascade of climate effects beginning at a global scale and ending at the level of individual life histories. This sheds light on how large-scale climate conditions substantially affect major life history parameters within a population, and thus influence key ecosystem parameters at the scale of centuries. [ABSTRACT FROM AUTHOR]

Background: Dorsal closing-wedge calcaneal osteotomy (DCWCO) is a treatment option for persistent Haglund exostosis-related heel pain after failed conservative management. In modifying the orientation of the calcaneal tendinous insertion site and reducing mechanical stress, the consequences of DCWCO-associated biomechanical changes on everyday foot function remain unknown., Methods: This retrospective cohort study analyzed routinely collected clinical data as well as data from our foot and ankle registry. One hundred twenty patients (66 males, 54 females, 17-77 years) who underwent DCWCO from January 2016 to December 2019 were included. Adverse events were collected from the patient files. Foot Function Index (FFI) scores were collected before (baseline) and at 6, 12, and 24 months postsurgery. Radiographic parameters including the Achilles tendon moment arm and X/Y ratio were evaluated from standard preoperative and 6-week postoperative radiographs. Correlations between FFI and biomechanical changes were calculated for men and women separately with the Pearson correlation coefficient and Bonferroni correction., Results: One intra- and 18 postoperative adverse events were documented. Mean baseline FFI pain decreased from 47.9 ± 17.2 to 12.0 ± 17.5 points at 24 months with an average decrease of -21.8 ± 21.3 points occurring within the first 6 months postsurgery. A similar trend was also seen with the FFI disability score (49.6 ± 20.3 to 12.8 ± 17.6 points). The mean decrease in Achilles tendon moment arm was -8.1 ± 3.8 mm and mean X/Y ratio increased from 2.6 ± 0.3 to 3.8 ± 1.0. There were no significant correlations between the FFI score and radiographic changes., Conclusion: DCWCO effectively alleviates exostosis-related heel pain and associated disabilities. Improvements can still be expected up to 2 years after surgery. Radiographic changes of the foot and ankle are significant but do not correlate with patient-reported outcome measures., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online.

Documentary climate data describe evidence of past climate arising from predominantly written historical documents such as diaries, chronicles, newspapers, or logbooks. Over the past decades, historians and climatologists have generated numerous document-based time series of local and regional climates. However, a global dataset of documentary climate time series has never been compiled, and documentary data are rarely used in large-scale climate reconstructions. Here, we present the first global multi-variable collection of documentary climate records. The dataset DOCU-CLIM comprises 621 time series (both published and hitherto unpublished) providing information on historical variations in temperature, precipitation, and wind regime. The series are evaluated by formulating proxy forward models (i.e., predicting the documentary observations from climate fields) in an overlapping period. Results show strong correlations, particularly for the temperature-sensitive series. Correlations are somewhat lower for precipitation-sensitive series. Overall, we ascribe considerable potential to documentary records as climate data, especially in regions and seasons not well represented by early instrumental data and palaeoclimate proxies., (© 2023. The Author(s).)

Annual-to-decadal variability in northern midlatitude temperature is dominated by the cold season. However, climate field reconstructions are often based on tree rings that represent the growing season. Here we present cold-season (October-to-May average) temperature field reconstructions for the northern midlatitudes, 1701-1905, based on extensive phenological data (freezing and thawing dates of rivers, plant observations). Northern midlatitude land temperatures exceeded the variability range of the 18th and 19th centuries by the 1940s, to which recent warming has added another 1.5 °C. A sequences of cold winters 1808/9-1815/6 can be explained by two volcanic eruptions and unusual atmospheric flow. Weak southwesterlies over Western Europe in early winter caused low Eurasian temperatures, which persisted into spring even though the flow pattern did not. Twentieth century data and model simulations confirm this persistence and point to increased snow cover as a cause, consistent with sparse information on Eurasian snow in the early 19th century., (© 2022. The Author(s).)

Malaria is an old scourge of humankind and has a large negative impact on the economic development of affected communities. Recent success in malaria control and reduction of mortality seems to have stalled emphasizing that our current intervention tools need to be complemented by malaria vaccines. Different populations of unconventional T cells such as mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells and γδ T cells are gaining attention in the field of malaria immunology. Significant advances in our basic understanding of unconventional T cell biology in rodent malaria models have been made, however, their roles in humans during malaria are less clear. Unconventional T cells are abundant in skin, gut and liver tissues, and long-lasting expansions and functional alterations were observed upon malaria infection in malaria naïve and malaria pre-exposed volunteers. Here, we review the current understanding of involvement of unconventional T cells in anti-Plasmodium falciparum immunity and highlight potential future research avenues.

Children from low- and middle-income countries, where there is a high incidence of infectious disease, have the greatest need for the protection afforded by vaccination, but vaccines often show reduced efficacy in these populations. An improved understanding of how age, infection, nutrition, and genetics influence immune ontogeny and function is key to informing vaccine design for this at-risk population. We sought to identify factors that shape immune development in children under 5 years of age from Tanzania and Mozambique by detailed immunophenotyping of longitudinal blood samples collected during the RTS,S malaria vaccine phase 3 trial. In these cohorts, the composition of the immune system is dynamically transformed during the first years of life, and this was further influenced by geographical location, with some immune cell types showing an altered rate of development in Tanzanian children compared to Dutch children enrolled in the Generation R population-based cohort study. High-titer antibody responses to the RTS,S/AS01E vaccine were associated with an activated immune profile at the time of vaccination, including an increased frequency of antibody-secreting plasmablasts and follicular helper T cells. Anemic children had lower frequencies of recent thymic emigrant T cells, isotype-switched memory B cells, and plasmablasts; modulating iron bioavailability in vitro could recapitulate the B cell defects observed in anemic children. Our findings demonstrate that the composition of the immune system in children varies according to age, geographical location, and anemia status., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Phenological data have become increasingly important as indicators of long-term climate change. Consequently, long-term homogeneity of the records is an important aspect. In this paper, we apply a breakpoint detection algorithm to the phenological series from the Swiss Phenology Network (SPN). A combination of three statistical tests is applied and different constraints are tested with respect to the choice of reference series. Breakpoint detection is only possible for a fraction of the series due to the shortness of some series and the lack of suitable reference series. Spring phases are more likely to be suitable than fall phases because of their higher spatial correlation. Out of nearly 3000 phenological series with at least 20 data points, only about 5% were found to be significantly inhomogeneous, although a visual validation indicates that many mid-sized breakpoints remained undetected. The detected breakpoints were compared with metadata and more than half of them could be attributed to a change of observer.

Our understanding of the human immune response to malaria remains incomplete. Clinical trials using whole-sporozoite-based vaccination approaches such as the Sanaria PfSPZ Vaccine, followed by controlled human malaria infection (CHMI) to assess vaccine efficacy offer a unique opportunity to study the immune response during Plasmodium falciparum infection. Diverse populations of T cells that are not restricted to classical HLA (unconventional T cells) participate in the host response during Plasmodium infection. Although several populations of unconventional T cells exist, the majority of studies focused on TCR Vγ9Vδ2 cells, the most abundant TCR γδ cell population in peripheral blood. In this study, we dissected the response of three TCR γδ cell subsets and mucosal-associated invariant T cells in healthy volunteers immunized with PfSPZ Vaccine and challenged by CHMI using Sanaria PfSPZ Challenge. Using a flow cytometry-based unbiased analysis followed by T cell cloning, several findings were made. Whereas major ex vivo alterations were not detectable after immunization with PfSPZ Vaccine, TCR Vδ2, and mucosal-associated invariant T cells expanded after asexual blood-stage parasitemia induced by CHMI. CHMI, but not vaccination, also induced the activation of TCR Vδ1 and Vδ1 - Vδ2 - γδ T cells. The activated TCR Vδ1 cells were oligoclonal, suggesting clonal expansion, and upon repeated CHMI, showed diminished response, indicating long-term alterations induced by blood-stage parasitemia. Some TCR Vδ1 clones recognized target cells in the absence of parasite-derived Ags, thus suggesting recognition of self-molecules. These findings reveal the articulate participation of different populations of unconventional T cells to P. falciparum infection., (Copyright © 2019 by The American Association of Immunologists, Inc.)

We are using controlled human malaria infection (CHMI) by direct venous inoculation (DVI) of cryopreserved, infectious Plasmodium falciparum (Pf) sporozoites (SPZ) (PfSPZ Challenge) to try to reduce time and costs of developing PfSPZ Vaccine to prevent malaria in Africa. Immunization with five doses at 0, 4, 8, 12, and 20 weeks of 2.7 × 10 5 PfSPZ of PfSPZ Vaccine gave 65% vaccine efficacy (VE) at 24 weeks against mosquito bite CHMI in U.S. adults and 52% (time to event) or 29% (proportional) VE over 24 weeks against naturally transmitted Pf in Malian adults. We assessed the identical regimen in Tanzanians for VE against PfSPZ Challenge. Twenty- to thirty-year-old men were randomized to receive five doses normal saline or PfSPZ Vaccine in a double-blind trial. Vaccine efficacy was assessed 3 and 24 weeks later. Adverse events were similar in vaccinees and controls. Antibody responses to Pf circumsporozoite protein were significantly lower than in malaria-naïve Americans, but significantly higher than in Malians. All 18 controls developed Pf parasitemia after CHMI. Four of 20 (20%) vaccinees remained uninfected after 3 week CHMI ( P = 0.015 by time to event, P = 0.543 by proportional analysis) and all four (100%) were uninfected after repeat 24 week CHMI ( P = 0.005 by proportional, P = 0.004 by time to event analysis). Plasmodium falciparum SPZ Vaccine was safe, well tolerated, and induced durable VE in four subjects. Controlled human malaria infection by DVI of PfSPZ Challenge appeared more stringent over 24 weeks than mosquito bite CHMI in United States or natural exposure in Malian adults, thereby providing a rigorous test of VE in Africa.

Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes in mucosal tissues and recognize a variety of riboflavin-related metabolites produced by the microbial flora. Relevant issues are whether MAIT cells are heterogeneous in the colon, and whether the local environment influences microbial metabolism thereby shaping MAIT cell phenotypes and responses. We found discrete MAIT cell populations in human colon, characterized by the diverse expression of transcription factors, cytokines and surface markers, indicative of activated and precisely controlled lymphocyte populations. Similar phenotypes were rare among circulating MAIT cells and appeared when circulating MAIT cells were stimulated with the synthetic antigens 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil, and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil. Furthermore, bacteria grown in colon-resembling conditions with low oxygen tension and harvested at stationary growth phase, potently activated human MAIT cells. The increased activation correlated with accumulation of the above antigenic metabolites as indicated by mass spectrometry. Thus, the colon environment contributes to mucosal immunity by directly affecting bacterial metabolism, and indirectly controlling the stimulation and differentiation of MAIT cells.

The Pan European Phenology (PEP) project is a European infrastructure to promote and facilitate phenological research, education, and environmental monitoring. The main objective is to maintain and develop a Pan European Phenological database (PEP725) with an open, unrestricted data access for science and education. PEP725 is the successor of the database developed through the COST action 725 "Establishing a European phenological data platform for climatological applications" working as a single access point for European-wide plant phenological data. So far, 32 European meteorological services and project partners from across Europe have joined and supplied data collected by volunteers from 1868 to the present for the PEP725 database. Most of the partners actively provide data on a regular basis. The database presently holds almost 12 million records, about 46 growing stages and 265 plant species (including cultivars), and can be accessed via http://www.pep725.eu/ . Users of the PEP725 database have studied a diversity of topics ranging from climate change impact, plant physiological question, phenological modeling, and remote sensing of vegetation to ecosystem productivity.

Comprehensive assessment of cellular responses to the RTS,S/AS01E vaccine is needed to understand potential correlates and ultimately mechanisms of protection against malaria disease. Cellular responses recognizing the RTS,S/AS01E-containing circumsporozoite protein (CSP) and Hepatitis B surface antigen (HBsAg) were assessed before and 1 month after primary vaccination by intracellular cytokine staining and 16-color flow cytometry in 105 RTS,S/AS01-vaccinated and 74 rabies-vaccinated participants (controls) in a pediatric phase III trial in Africa. RTS,S/AS01E-vaccinated children had significantly higher frequencies of CSP- and HBsAg-specific CD4 + T cells producing IL-2, TNF-α, and CD40L and HBsAg-specific CD4 + T producing IFN-γ and IL-17 than baseline and the control group. Vaccine-induced responses were identified in both central and effector memory (EM) compartments. EM CD4 + T cells expressing IL-4 and IL-21 were detected recognizing both vaccine antigens. Consistently higher response rates to both antigens in RTS,S/AS01E-vaccinated than comparator-vaccinated children were observed. RTS,S/AS01E induced polyfunctional CSP- and HBsAg-specific CD4 + T cells, with a greater degree of polyfunctionality in HBsAg responses. In conclusion, RTS,S/AS01E vaccine induces T cells of higher functional heterogeneity and polyfunctionality than previously characterized. Responses detected in memory CD4 + T cell compartments may provide correlates of RTS,S/AS01-induced immunity and duration of protection in future correlates of immunity studies.

The impact of spring temperature forcing on the timing of leaf unfolding of plants (temperature sensitivity, S T ) is one important indicator of how and to what degree plant species track climate change. Fu et al. (Nature 526:104-107, 2015) found that S T has significantly decreased from the 1980-1994 to the 1999-2013 period for seven mid-latitude tree species in Europe. However, long-term changes in S T over the past 60 years are still not clear. Here, using in situ observations of leaf unfolding for seven dominant European tree species, we analyze the temporal change in S T over decadal time scales extending the data series back to 1951. Our results demonstrate that S T shows no statistically significant change within shifting 30-year windows from 1951 to 2013 and remains stable between 1951-1980 and 1984-2013 (3.6 versus 3.7 days °C -1 ). This result suggests that the significant decrease in S T over the past 33 years could not be sustained when examining the trends of phenological responses in the long run. Therefore, we could not conclude that tree spring phenology advances will slow down in the future, and the S T changes in warming scenarios are still uncertain.

Temperature sensitivity of plant phenology (S T ) is a determining factor of as to what degree climate change impacts on plant species. Fu et al . (Int J Biometeorol 60:1611-1613, 2016) claimed that long long-term linear trends mask phenological shifts. However, the decreased and increased S T was both found in warming scenarios. The conceptual scheme telling the nonlinear relationship between spring temperature and leaf unfolding date proposed by Fu et al . (Int J Biometeorol 60:1611-1613, 2016) cannot be supported by observation data across Europe. Therefore, linking declined S T to climate warming is misleading, and future S T changes are more uncertain than they suggested.

Existing evidence of plant phenological change to temperature increase demonstrates that the phenological responsiveness is greater at warmer locations and in early-season plant species. Explanations of these findings are scarce and not settled. Some studies suggest considering phenology as one functional trait within a plant's life history strategy. In this study, we adapt an existing phenological model to derive a generalized sensitivity in space (SpaceSens) model for calculating temperature sensitivity of spring plant phenophases across species and locations. The SpaceSens model have three parameters, including the temperature at the onset date of phenophases (Tp), base temperature threshold (Tb) and the length of period (L) used to calculate the mean temperature when performing regression analysis between phenology and temperature. A case study on first leaf date of 20 plant species from eastern China shows that the change of Tp and Tb among different species accounts for interspecific difference in temperature sensitivity. Moreover, lower Tp at lower latitude is the main reason why spring phenological responsiveness is greater there. These results suggest that spring phenophases of more responsive, early-season plants (especially in low latitude) will probably continue to diverge from the other late-season plants with temperatures warming in the future.

The change in the phenology of plants or animals reflects the response of living systems to climate change. Numerous studies have reported a consistent earlier spring phenophases in many parts of middle and high latitudes reflecting increasing temperatures with the exception of China. A systematic analysis of Chinese phenological response could complement the assessment of climate change impact for the whole Northern Hemisphere. Here, we analyze 1263 phenological time series (1960-2011, with 20+ years data) of 112 species extracted from 48 studies across 145 sites in China. Taxonomic groups include trees, shrubs, herbs, birds, amphibians and insects. Results demonstrate that 90.8% of the spring/summer phenophases time series show earlier trends and 69.0% of the autumn phenophases records show later trends. For spring/summer phenophases, the mean advance across all the taxonomic groups was 2.75 days decade(-1) ranging between 2.11 and 6.11 days decade(-1) for insects and amphibians, respectively. Herbs and amphibians show significantly stronger advancement than trees, shrubs and insect. The response of phenophases of different taxonomic groups in autumn is more complex: trees, shrubs, herbs and insects show a delay between 1.93 and 4.84 days decade(-1), while other groups reveal an advancement ranging from 1.10 to 2.11 days decade(-1) . For woody plants (including trees and shrubs), the stronger shifts toward earlier spring/summer were detected from the data series starting from more recent decades (1980s-2000s). The geographic factors (latitude, longitude and altitude) could only explain 9% and 3% of the overall variance in spring/summer and autumn phenological trends, respectively. The rate of change in spring/summer phenophase of woody plants (1960s-2000s) generally matches measured local warming across 49 sites in China (R=-0.33, P<0.05)., (© 2014 John Wiley & Sons Ltd.)

Animal microRNAs (miRNA) are implicated in the control of nearly all cellular functions. Due to high sequence redundancy within the miRNA gene pool, loss of most of these 21- to 24-bp long RNAs individually does not cause a phenotype. Thus, only very few miRNAs have been associated with clear functional roles. We constructed a transgenic UAS-miRNA library in Drosophila melanogaster that contains 180 fly miRNAs. This library circumvents the redundancy issues by facilitating the controlled misexpression of individual miRNAs and is a useful tool to complement loss-of-function approaches. Demonstrating the effectiveness of our library, 78 miRNAs induced clear phenotypes. Most of these miRNAs were previously unstudied. Furthermore, we present a simple system to create GFP sensors to monitor miRNA expression and test direct functional interactions in vivo. Finally, we focus on the miR-92 family and identify a direct target gene that is responsible for the specific wing phenotype induced by the misexpression of miR-92 family members.

Mankind has observed and documented life cycle stages of plants and animals for a long time. However, it was comparatively recently that the newly emerging science was given its name. The name of Charles Morren and the year 1853 are being cited, although not frequently. Exact information is hardly known among present-day phenologists, yet new evidence shows that the term "phenology" was already in use in 1849. In the early 1840s, physicist and astronomer Adolphe Quetelet set up an observational network named "Observations of periodical Phenomena of the Animal and Vegetable Kingdom" and issued instructions for it. Even though biologist Charles Morren welcomed Quetelet's initiative, differences between Morren and Quentlet regarding the instructions for the observations and the potential results soon arose and a debate started, which lasted for nearly 10 years. In the wake of these disagreements, Morren was compelled to create a new term to denote his ideas on "periodical phenomena". At first, he temporally used the word anthochronology, but in the end he coined the word phenology. The term was first used in a public lecture at the Académie royale des Sciences, des Lettres et des Beaux-Arts de Belgique' in Brussels on 16 December 1849, and simultaneously in the December 1849 issue of volume V of the Annales de la Société royale d'Agriculture et de Botanique de Gand. One had to wait until 1853 before the new name appeared in the title of one of Morren's publications. Based on evidence from archives and original publications, we trace the 10-year-long scientific debate between Morren and Quetelet. Morren states his biologist's view on the subject and extends the more climate-related definition of Quetelet of "periodical phenomena".