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Abstract In this study, we experimentally addressed the impact of different pollination treatments on the morphological, reproductive and chemical traits of fruits and seeds of two crop species, the wild strawberry (Fragaria vesca L.) and cowpea (Vigna unguiculata (L.) Walp.). Multiple flowers from each plant were exposed to different pollination treatments: (1) self pollination, (2) hand cross pollination and (3) open pollination. Both crops were positively affected by open pollination in terms of morpho-chemical parameters concerning the marketability (e.g., 35% decrease in sugar/acid ratio in open pollinated strawberries compared to the autogamous ones) and the seed germination rate as a proxy of reproduction efficiency (e.g., the almost complete absence of seed abortion in the open pollination treatment). Remarkably, the pollination treatment also strongly influenced the phytochemical composition. Open-pollinated strawberries exhibited a higher relative concentration of compounds endowed with nutraceutical properties such as anthocyanins, ellagic acid derivatives and flavonoids. At the same time, cowpea seeds displayed higher concentrations of anti-nutrients in the self pollination treatments, such as saponins, compared to the open and hand cross pollinated seeds. This study suggests the presence of a link between the pollination mechanism, market quality, plant reproduction and chemical properties of fruits and seeds, supporting the intricate interplay between pollinators, plants and human nutrition, highlighting the crucial importance of animal pollination in the ecological and dietary contexts.

Droughts are often long-lasting phenomena, without a distinct start or end and with impacts cascading across sectors and systems, creating long-term legacies. Nevertheless, our current perceptions and management of droughts and their impacts are often event-based, which can limit the effective assessment of drought risks and reduction of drought impacts. Here, we advocate for changing this perspective and viewing drought as a hydrological–ecological–social continuum. We take a systems theory perspective and focus on how “memory” causes feedback and interactions between parts of the interconnected systems at different timescales. We first discuss the characteristics of the drought continuum with a focus on the hydrological, ecological, and social systems separately, and then we study the system of systems. Our analysis is based on a review of the literature and a study of five cases: Chile, the Colorado River basin in the USA, northeast Brazil, Kenya, and the Rhine River basin in northwest Europe. We find that the memories of past dry and wet periods, carried by both bio-physical (e.g. groundwater, vegetation) and social systems (e.g. people, governance), influence how future drought risk manifests. We identify four archetypes of drought dynamics: impact and recovery, slow resilience building, gradual collapse, and high resilience–big shock. The interactions between the hydrological, ecological, and social systems result in systems shifting between these types, which plays out differently in the five case studies. We call for more research on drought preconditions and recovery in different systems, on dynamics cascading between systems and triggering system changes, and on dynamic vulnerability and maladaptation. Additionally, we advocate for more continuous monitoring of drought hazards and impacts, modelling tools that better incorporate memories and adaptation responses, and management strategies that increase societal and institutional memory. This will help us to better deal with the complex hydrological–ecological–social drought continuum and identify effective pathways to adaptation and mitigation.

Abstract Background Glioblastoma (GBM) stands as the most prevalent and aggressive form of adult gliomas. Despite the implementation of intensive therapeutic approaches involving surgery, radiation, and chemotherapy, Glioblastoma Stem Cells contribute to tumor recurrence and poor prognosis. The induction of Glioblastoma Stem Cells differentiation by manipulating the transcriptional machinery has emerged as a promising strategy for GBM treatment. Here, we explored an innovative approach by investigating the role of the depolarized resting membrane potential (RMP) observed in patient-derived GBM sphereforming cell (GSCs), which allows them to maintain a stemness profile when they reside in the G0 phase of the cell cycle. Methods We conducted molecular biology and electrophysiological experiments, both in vitro and in vivo, to examine the functional expression of the voltage-gated sodium channel (Nav) in GSCs, particularly focusing on its cell cycle-dependent functional expression. Nav activity was pharmacologically manipulated, and its effects on GSCs behavior were assessed by live imaging cell cycle analysis, self-renewal assays, and chemosensitivity assays. Mechanistic insights into the role of Nav in regulating GBM stemness were investigated through pathway analysis in vitro and through tumor proliferation assay in vivo. Results We demonstrated that Nav is functionally expressed by GSCs mainly during the G0 phase of the cell cycle, suggesting its pivotal role in modulating the RMP. The pharmacological blockade of Nav made GBM cells more susceptible to temozolomide (TMZ), a standard drug for this type of tumor, by inducing cell cycle re-entry from G0 phase to G1/S transition. Additionally, inhibition of Nav substantially influenced the self-renewal and multipotency features of GSCs, concomitantly enhancing their degree of differentiation. Finally, our data suggested that Nav positively regulates GBM stemness by depolarizing the RMP and suppressing the ERK signaling pathway. Of note, in vivo proliferation assessment confirmed the increased susceptibility to TMZ following pharmacological blockade of Nav. Conclusions This insight positions Nav as a promising prognostic biomarker and therapeutic target for GBM patients, particularly in conjunction with temozolomide treatment.

Cold-adapted species endangered by global change are crucial cases for understanding range dynamics and its interface with conservation and environmental decision-making. However, the study of their distribution change is either neglected or conducted at coarse resolutions at continental level, thus having little indicator value for regional and local conservation strategies. In view of climate change, it can be expected that cold-adapted insects should reduce distribution ranges by mainly concentric retreats and moving uphill. To test these hypotheses, we targeted four threatened, high-altitude bumblebees differing in subgenera and elevation ranges, and covering the main central and south European mountains. We performed species distribution models including climate and habitat at a 1 km-resolution, and we estimated elevation uphill and the year of elevation change with broken-line regressions. Results indicate that climate change will likely cause severe future range contractions across large areas, more in the Apennines (80 %–85 % ca) than the Alps and Pyrenees (24–56 % ca), with mostly concentric retreats as future extents will nearly entirely be included in the present ones. Remarkably, since the ‘80 s elevation uplift has started by about 325–535 m, a period coinciding with the beginning of the main warming, and will continue. The size and distribution of climate refugia will challenge conservation: they will be small (2–60 % of current areas) and even vary regionally, but while in the Apennines and Pyrenees they will be nearly entirely within Protected Areas, only a third will be so for the Alps. Such impressive distribution and elevation changes demonstrate that cold-adapted bumblebees can track climate change, reasons for it to be found in the specialist niches mainly requiring narrow temperature ranges and glacier presence. Overall, the distribution changes of cold specialist bumblebees driven by climate change demonstrate that conservation and policy makers should act upon the time dynamics and regional responses because future range contraction, the little availability of new areas and the movement uphill emerge as consistent patterns.

Lysosomal Ca2+ signaling is emerging as a crucial regulator of endothelial Ca2+ dynamics. Ca2+ release from the acidic vesicles in response to extracellular stimulation is usually promoted via Two Pore Channels (TPCs) and is amplified by endoplasmic reticulum (ER)-embedded inositol-1,3,4-trisphosphate (InsP3) receptors and ryanodine receptors. Emerging evidence suggests that sub-cellular Ca2+ signals in vascular endothelial cells can also be generated by the Transient Receptor Potential Mucolipin 1 channel (TRPML1) channel, which controls vesicle trafficking, autophagy and gene expression. Herein, we adopted a multidisciplinary approach, including live cell imaging, pharmacological manipulation, and gene targeting, revealing that TRPML1 protein is expressed and triggers global Ca2+ signals in the human brain microvascular endothelial cell line, hCMEC/D3. The direct stimulation of TRPML1 with both the synthetic agonist, ML-SA1, and the endogenous ligand phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) induced a significant increase in [Ca2+]i, that was reduced by pharmacological blockade and genetic silencing of TRPML1. In addition, TRPML1-mediated lysosomal Ca2+ release was sustained both by lysosomal Ca2+ release and ER Ca2+- release through inositol-1,4,5-trisphophate receptors and store-operated Ca2+ entry. Notably, interfering with TRPML1-mediated lysosomal Ca2+ mobilization led to a decrease in the free ER Ca2+ concentration. Imaging of DAF-FM fluorescence revealed that TRPML1 stimulation could also induce a significant Ca2+-dependent increase in nitric oxide concentration. Finally, the pharmacological and genetic blockade of TRPML1 impaired ATP-induced intracellular Ca2+ release and NO production. These findings, therefore, shed novel light on the mechanisms whereby the lysosomal Ca2+ store can shape endothelial Ca2+ signaling and Ca2+-dependent functions in vascular endothelial cells.

The area sourrounding the Mediterranean basin is recognised as a major biodiversity hotspot for bees, and Italy is amongst the European countries with the highest bee species richness. Detailed knowledge of bee distribution is crucial for understanding bee biology and designing tailored conservation strategies, but is still insufficient in southern European countries, especially in Italy.We report recent finds of 48 bee species that yield significant novelties for the Italian bee fauna. Eight species, namely Andrena confinis Stöckhert, Anthidiellum breviusculum Pérez, Coelioxys alatus Foerster, Lasioglossum algericolellum Strand, Megachile lapponica Thomson, Megachile opacifrons Pérez, Megachile semicircularis auct. nec Zanden and Trachusa integra Eversmann are reported as new for Italy. In addition, Andrena binominata Smith, Andrena compta Lepeletier, Colletes acutus Pérez, Lasioglossum strictifrons Vachal, Rhodanthidium siculum Spinola and Rhodanthidium sticticum Fabricius are newly recorded from mainland Italy, Osmia heteracantha Pérez from Sardegna and Nomada flavopicta Kirby from Sicilia. We also report significant range extensions for other bee species and recent records of species that had long gone unrecorded in Italy. The combination of morphology and DNA barcoding provided reliable identifications even for the most challenging specimens. As several of our records come from areas neglected by bee experts in the past, this study stands out as a key indicator of a bee faunistic richness still awaiting discovery and hopefully it will stimulate the interest of taxonomists and stakeholders in pursuing bee research in Italy in the near future.

Abstract Pollinator insects are declining worldwide, also due to the alteration of their diet with severe implications on their health status. Pollinators diet relies mainly on flower rewards (i.e. pollen and nectar), and a precise characterization of their chemical composition is crucial in defining pollinators' nutritional ecology. In this context, the pollen represents a challenging source to investigate, especially due to operative challenges during collection operations and to the small amounts produced per flower. Here, we designed and tested a novel, easy‐to‐assemble tool for pollen sampling: E‐PoSa (Electronic Pollen Sampler), based on the use of a portable vacuum cleaner. We compared it with some of the most used sampling methods for pollen (i.e. anthers sieving and sampling of the whole anthers) by looking at the differences in their quantitative recovery and nutritional profile. Its applicability in ecological studies was also corroborated by an assessment of its recovery rate obtained from a panel of wildflower species in an operational environment. The data obtained showed a significantly higher pollen recovery capacity of E‐PoSa compared with the conventional sieving approach and the success in retrieving enough pollen to conduct phytochemical analyses from a broad range of flower morphologies in the field. Our results also demonstrated that high purity pollen can be collected with E‐PoSa and that the device does not introduce any significant variation in the nutritional analysis compared with the conventional sieving. This new sampling approach represents a cheap and easy‐to‐assemble tool encouraging its future use not only in the field of pollen nutrition but also in a wide variety of other contexts related to pollination ecology. Acknowledging the potential influences of the sampling techniques and moving towards shared standardized field protocols will advance the comprehension of species interactions and foraging patterns of pollinators and their nutritional needs.

The objective of the present study was to examine if the Outcome Bias also occurs in pilots flying under instrument flight rules (IFR). In a scenario-based survey, 60 pilots evaluated weather-related decisions made by hypothetical pilots. Participants rated the decisions as better, less risky, and regarded the probability that they would have made the same decision as higher when they were followed by a positive outcome, than when they were followed by a negative outcome. This effect showed likewise for novice pilots and for experienced pilots. These findings could be relevant for the flight-related decision-making of pilots, which sometimes is affected by the decisions made by third-party pilots. In particular, decisions made by other pilots that have led to positive outcomes might be hastily followed, whereas those that have led to negative outcomes might be hastily rejected.

Developing and implementing climate adaptation measures in complex socio-ecological systems can lead to unintended consequences, especially when those systems are undergoing rapid hydro-climatic and socio-economic change. In these dynamic contexts, a systemic approach can make the difference between adaptive and maladaptive outcomes. This paper focuses on the use of climate services, often touted as no-regret solutions, and their potential to generate maladaptation. We explored the interactions between climate services and adaptation/maladaptation across five case studies affected by different types of natural hazards and characterized by a range of hydro-climatic and socio-economic conditions. Using system archetypes, we show how climate services can play a role in both producing and preventing maladaptation. The dynamics explored through system archetypes are: i) “fixes that fail”, where short-sighted solutions fail to address the root causes of a problem; ii) “band aid solutions”, where the benefits brought about in the short-term come at the expenses of delaying long-term adaptive actions; and iii) “success to the successful”, where some groups increasingly benefit from climate services at the expenses of other groups. We demonstrate how these dynamics constitute maladaptive processes, as well as identifying the tools and theories that can be used in this type of assessment. Finally, we provide a framework and recommendations to guide the ex-ante assessment of maladaptation risk when designing and implementing climate services.

One of the most vulnerable phases in the plant life cycle is sexual reproduction, which depends on effective pollen transfer, but also on the thermotolerance of pollen grains. Pollen thermotolerance is temperature-dependent and may be reduced by increasing temperature associated with global warming. A growing body of research has focused on the effect of increased temperature on pollen thermotolerance in crops to understand the possible impact of temperature extremes on yield. Yet, little is known about the effects of temperature on pollen thermotolerance of wild plant species. To fill this gap, we selected Lotus corniculatus s.l. (Fabaceae), a species common to many European habitats and conducted laboratory experiments to test its pollen thermotolerance in response to artificial increase in temperature. To test for possible local adaptation of pollen thermal tolerance, we compared data from six lowland (389–451 m a.s.l.) and six highland (841–1,030 m a.s.l.) populations. We observed pollen germination in vitro at 15 °C, 25 °C, 30 °C, and 40 °C. While lowland plants maintained a stable germination percentage across a broad temperature range (15–30 °C) and exhibited reduced germination only at extremely high temperatures (40 °C), highland plants experienced reduced germination even at 30 °C–temperatures commonly exceeded in lowlands during warm summers. This suggests that lowland populations of L. corniculatus may be locally adapted to higher temperature for pollen germination. On the other hand, pollen tube length decreased with increasing temperature in a similar way in lowland and highland plants. The overall average pollen germination percentage significantly differed between lowland and highland populations, with highland populations displaying higher germination percentage. On the other hand, the average pollen tube length was slightly smaller in highland populations. In conclusion, we found that pollen thermotolerance of L. corniculatus is reduced at high temperature and that the germination of pollen from plant populations growing at higher elevations is more sensitive to increased temperature, which suggests possible local adaptation of pollen thermotolerance.

Abstract Pollinator insects are declining worldwide also due to the alteration of their diet which plays a pivotal role in influencing their health status. Despite interspecific and intraspecific diversity in the diet, pollinators completely or partly rely on pollen and nectar as food sources. A precise characterization of the chemical composition of these flower resources represents a key step in the definition of pollinators' nutritional ecology. However, pollen and nectar represent challenging sources to collect and analyze, especially due to their small amounts per flower, and the application of suitable sampling and analysis tools is a pivotal step to perform dedicated studies and comparisons. Here, we compared a recently proposed tool based on a portable vacuum cleaner for floral pollen collection (E‐PoSa, i.e., Electronic Pollen Sampler) with traditional pollen sampling methods (i.e., anther collection and anther sieving) together with the evaluation of different nectar sampling techniques (i.e., centrifugation, microcapillaries, washing, and microrinsing) by looking at the differences in their quantitative recovery as well as their chemical profiling. Pollen and nectar were collected from three model flower species each. Our results demonstrated that different collection methods introduce biases in the nutritional profiling of floral rewards and specifically: (1) underestimation of the pollen protein and lipid content in the anther collection method; (2) reduction in the volume of recovered nectar by centrifugation; (3) overestimation of the glucose content in the nectar collected by flower washing and underestimation of the glucose content by microrinsing; and (4) relevant biases in the phytochemical profiles of pollen and nectar by analyzing the whole anthers and the nectar collected by washing the entire flower. Differences in methods were not directly related to the different productivity of pollen and nectar across species. The final goal of the study is to propose standardized, comparable, and easily accessible strategies for the study of flower resources that ultimately impact on pollinators' nutritional ecology. Acknowledging the potential influences of the sampling techniques and moving toward shared field protocols will advance the comprehension of species interactions, foraging patterns, and pollinators' nutritional needs.

IntroductionCACNA1S related congenital myopathy is an emerging recently described entity. In this report we describe 2 sisters with mutations in the CACNA1S gene and the novel phenotype of congenital myopathy and infantile onset episodic weakness.Clinical descriptionBoth sisters had neonatal onset hypotonia, muscle weakness, and delayed walking. Episodic weakness started in infancy and continued thereafter, provoked mostly by cold exposure. Muscle imaging revealed fat replacement of gluteus maximus muscles. Next generation sequencing found the missense p.Cys944Tyr variant and the novel splicing variant c.3526-2A>G in CACNA1S. Minigene assay revealed the splicing variant caused skipping of exon 28 from the transcript, potentially affecting protein folding and/or voltage dependent activation.ConclusionThis novel phenotype supports the notion that there are age related differences in the clinical expression of CACNA1S gene mutations. This expands our understanding of mutations located in regions of the CACNA1S outside the highly conserved S4 segment, where most mutations thus far have been identified.

On August 13-14, 2019, the Healthcare Nutrition Council and the ASN held the Medical Foods Workshop: Science, Regulation, and Practical Aspects. Medical food products help patients manage their disease and improve their quality of life. Yet many hurdles exist to getting patients new products. In this workshop, participants addressed some of these hurdles, with specific emphasis on topics like the statutory term distinctive nutritional requirements, the regulatory term modification of the diet alone, the role of clinical guidelines, the requirement that medical foods be used under medical supervision, and differentiation of foods for special dietary use from medical foods, as well as product innovation and future research. Real-world examples were discussed for intractable epilepsy, diabetes, end-stage renal disease, and inflammatory bowel disease.

Introdução: A psoríase é uma doença crônica, inflamatória, imunomediada, cujos pacientes apresentam alto risco de comorbidades. O consenso da Sociedade Brasileira de Dermatologia recomenda o atingimento de PASI 90/100 como meta terapêutica, desfechos que estão associados com a melhora da satisfação com o tratamento e da qualidade de vida do paciente. Objetivos: Avaliar o custo-efetividade (CEA) e o impacto orçamentário (AIO) do tratamento com Risanquizumabe (RZB) em comparação à Adalimumabe, Etanercepte, Guselcumabe, Infliximabe, Ixequizumabe, Secuquinumabe e Ustequinumabe, imunobiológicos previamente disponíveis no Sistema Suplementar de Saúde (SSS), para o tratamento da psoríase em placas moderada a grave em pacientes que não responderam à terapia prévia com não-biológicos. Material e Método: Foram avaliados os custos do tratamento da psoríase com biológicos e eventuais eventos adversos. Foi realizada análise de custo-utilidade para estimar o custo por Anos de Vida ajustados pela Qualidade (QALY) de RZB comparado aos imunobiológicos previamente incluídos no SSS em relação ao atingimento de PASI 90/100. Adotou-se modelo híbrido contendo uma árvore de decisão apresentando a resposta primária e uma coorte baseada de Markov contemplando três estados de saúde: (1) resposta terapêutica com manutenção da terapia do imunobiológico; (2) falha terapêutica, ocorrendo o uso de outro imunobiológico; (3)óbito. Pacientes respondedores no período de indução entraram no estado de saúde 1, permanecendo até falha terapêutica ou óbito. Após falha pacientes migraram para o estado de saúde 2 junto com os que falharam no período de resposta primária e permaneceram até o óbito. A AIO foi desenvolvida considerando diferentes cenários para o RZB e competidores. Resultados: Em CEA o RZB demonstrou eficácia superior e custos inferiores (dominância) quando comparado a cinco dos imunobiológicos avaliados, no cenário base [economia vs: infliximabe (-R$ 3.740,59); secuquinumabe (- R$ 9.170,13); ixequizumabe (-R$ 21.254,37); ustequinumabe (-R$ 23.652,00); guselcumabe (-R$ 31.470,26)], e demonstrou maior custo e maior efetividade/utilidade em relação a adalimumabe e etanercepte em metade das análises de sensibilidade probabilística. AIO demonstrou economia superior a R$34 milhões em 5 anos (CMED2021). Discussão e Conclusões: RZB demonstrou ser custo-efetivo com posologia conveniente para os pacientes. A AIO revelou que RZB proporciona economia em todos os cenários analisados, contribuindo com a sustentabilidade do SSS brasileiro.

Perovskite oxides have garnered immense interest across diverse fields owing to their exceptional properties. Among these, SrTiO3 is an excellent photocatalyst under UV light and boasts remarkable thermal stability, rendering it ideal for high-temperature applications. While various synthesis methods exist for SrTiO3, prioritizing environmentally friendly processes, even at the laboratory scale, remains crucial.This study introduces a pioneering life cycle assessment (LCA) comparing six SrTiO3 synthesis techniques (solid-state reaction, sonochemical, sol–gel, hydrothermal, solvothermal, and molten-salt) to gauge their environmental impacts, pinpoint potential concerns, and offer insights for the future. Interestingly, methods like molten salt and sol–gel display higher pollution tendencies due to significant energy usage, particularly during drying and calcination stages. Conversely, the solid-state reaction and ultrasound-assisted methods emerge as sustainable pathways for crafting environmentally conscious SrTiO3 materials. Significantly, electricity emerges as a pivotal factor influencing environmental impact, urging the exploration of alternatives and the need for strategic decisions. This investigation not only sheds light on the ecological footprint of SrTiO3 synthesis but also underscores the urgency for adopting greener approaches in materials manufacturing.