Substantia nigra activity level predicts trial-to-trial adjustments in cognitive control

Effective adaptation to the demands of a changing environment requires flexible cognitive control. The medial and the lateral frontal cortices are involved in such control processes, putatively in close interplay with the BG. In particular, dopaminergic projections from the midbrain (i.e., from the substantia nigra [SN] and the ventral tegmental area) have been proposed to play a pivotal role in modulating the activity in these areas for cognitive control purposes. In that dopaminergic involvement has been strongly implicated in reinforcement learning, these ideas suggest functional links between reinforcement learning, where the outcome of actions shapes behavior over time, and cognitive control in a more general context, where no direct reward is involved. Here, we provide evidence from functional MRI in humans that activity in the SN predicts systematic subsequent trial-to-trial RT prolongations that are thought to reflect cognitive control in a stop-signal paradigm. In particular, variations in the activity level of the SN in one trial predicted the degree of RT prolongation on the subsequent trial, consistent with a modulating output signal from the SN being involved in enhancing cognitive control. This link between SN activity and subsequent behavioral adjustments lends support to theoretical accounts that propose dopaminergic control signals that shape behavior both in the presence and in the absence of direct reward. This SN-based modulatory mechanism is presumably mediated via a wider network that determines response speed in this task, including frontal and parietal control regions, along with the BG and the associated subthalamic nucleus

Characterisation of the aroma of green mexican coffee and identification of mouldy/earthy defect

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)The aromas of a reference green Mexican coffee (Arabica) and of a coffee from the same origin, but having a pronounced earthy/mouldy off-taint, were characterised. From comparison of the two aroma profiles, the compounds causing the defect were detected by gas chromatography olfactometry, isolated and concentrated by preparative bi-dimensional gas chromatography, and characterised by gas chromatography mass spectrometry. Six compounds participated in the off-flavour. Geosmin, 2-methylisoborneol, 2,4,6-trichloroanisole were found to be the main culprits, while three methoxy pyrazines (2-methoxy-3-isopropyl/-3-sec-butyl/-3-isobutyl pyrazine) contributed to a lesser extent to the earthy/ green undertone. The occurrence of the off-flavour could tentatively be linked to post-harvest drying

Passive Wrist Stiffness: The Influence of Handedness

Objective: This paper reports on the quantification of passive wrist joint stiffness and investigates the potential influence of handedness and gender on stiffness estimates. Methods: We evaluated the torque-angle relationship during passive wrist movements in 2 degrees of freedom (into flexion-extension and radial-ulnar deviation) in 13 healthy subjects using a wrist robot. Experimental results determined intrasubject differences between dominant and nondominant wrist and intersubject differences between male and female participants. Results: We found differences in the magnitude of passive stiffness of left- and right-hand dominant males and right-hand dominant females suggesting that the dominant hand tends to be stiffer than the nondominant hand. Left-hand stiffness magnitude was found to be 37% higher than the right-hand stiffness magnitude in the left-handed male group and the right-hand stiffness magnitude was 11% and 40% higher in the right-handed male and female groups, respectively. Other joint stiffness features such as the orientation and the anisotropy of wrist stiffness followed the expected pattern from previous studies. Conclusion: The observed difference in wrist stiffness between the dominant and nondominant limb is likely due to biomechanical adaptations to repetitive asymmetric activities (such as squash, tennis, basketball, or activities of daily living such as writing, teeth brushing, etc.). Significance: Understanding and quantifying handedness influence on stiffness may have critical implication for the optimization of surgical and rehabilitative interventions

Novel Insights into the Bovine Polled Phenotype and Horn Ontogenesis in Bovidae

Despite massive research efforts, the molecular etiology of bovine polledness and the developmental pathways involved in horn ontogenesis are still poorly understood. In a recent article, we provided evidence for the existence of at least two different alleles at the Polled locus and identified candidate mutations for each of them. None of these mutations was located in known coding or regulatory regions, thus adding to the complexity of understanding the molecular basis of polledness. We confirm previous results here and exhaustively identify the causative mutation for the Celtic allele (PC) and four candidate mutations for the Friesian allele (PF). We describe a previously unreported eyelash-and-eyelid phenotype associated with regular polledness, and present unique histological and gene expression data on bovine horn bud differentiation in fetuses affected by three different horn defect syndromes, as well as in wild-type controls. We propose the ectopic expression of a lincRNA in PC/p horn buds as a probable cause of horn bud agenesis. In addition, we provide evidence for an involvement of OLIG2, FOXL2 and RXFP2 in horn bud differentiation, and draw a first link between bovine, ovine and caprine Polled loci. Our results represent a first and important step in understanding the genetic pathways and key process involved in horn bud differentiation in Bovidae

Simultaneous eradications of Black Rat (Rattus rattus) and Ice plants (Carpobrotus spp.) on Bagaud Island (Port-Cros National Park, Provence, France): preliminary results on their impacts on Athropods communities

Les invasions biologiques sont reconnues comme l’une des principales menaces pour la conservation de la biodiversité, et de nombreux travaux ont été conduits à travers la planète pour restaurer la biodiversité insulaire par des programmes d’éradication d’espèces invasives. Cependant, peu d’études scientifiques post-éradication ont été conduites notamment pour l’évaluation de la biodiversité des communautés d’Arthropodes. L’île de Bagaud, située dans l’archipel des îles d’Hyères (Var, France), est une réserve intégrale du Parc national de Port-Cros (PNPC) qui a notamment été soumise à deux perturbations majeures d’origine anthropique au cours des derniers siècles : l’invasion du Rat noir (Rattus rattus) et celle des Griffes de sorcière (Carpobrotus spp.). Ces espèces allochtones engendrent des effets particulièrement néfastes sur la flore et la faune des écosystèmes insulaires méditerranéens, notamment sur les Arthropodes. Le PNPC a ainsi lancé un programme décennal de restauration écologique qui implique l’éradication de ces deux taxons invasifs. La communauté des Arthropodes de l’île a fait l’objet d’un état initial au printemps 2011, les éradications ont été effectuées entre septembre 2011 et janvier 2013, et la première campagne d’échantillonnage post-éradication a été réalisée au printemps 2013. L’échantillonnage de la faune épigée a été réalisé au moyen de quatre transects fixes de pièges Barber répartis dans différents milieux écologiques de l’île. Cette première étude post-éradication révèle une augmentation de l’abondance des Arthropodes piégés entre 2011 (4868 individus dans 74 pièges) et 2013 (6892, n = 60). Les effectifs moyens par piège augmentent significativement dans les zones où les Carpobrotus spp. ont été arrachés, mais chutent dans la zone de maquis qui abritait une forte densité de R. rattus. La richesse spécifique reste globalement stable (220 morpho-espèces en 2011, 216 en 2013), cependant les communautés de décomposeurs explosent a contrario des populations de prédateurs. Les suivis doivent être poursuivis afin de mieux déterminer les impacts directs et indirects à long terme de ces éradications s’exerçant sur la biodiversité des communautés d’Arthropodes de l’île.Biological invasions are recognized as one of the major threats to island biodiversity conservation, and numerous studies have been conducted around the world to restore the biodiversity of islands submitted to invasive species impacts. However, few scientific post-eradication studies were piloted notably for the biodiversity assessment of Arthropod communities. Bagaud Island is an integral reserve of the Port-Cros National Park (PNPC), located in the îles d’Hyères Archipelago (Var, France). In the last centuries, it has undergone two major anthropogenic disturbances: the invasion of the Black Rat (Rattus rattus) and the Ice plants (Carpobrotus spp.), two alien taxa known for their particularly negative effects on the flora and fauna of the Mediterranean island ecosystems, including Arthropods. PNPC has launched a ten-year program of ecological restoration that involves the eradication of these two invasive taxa. The Arthropod communities of the island have been analysed in their initial state in spring 2011, eradications were conducted between September 2011 and January 2013, and the first post-eradication campaign began in spring 2013. The ground fauna was sampled using four transects of Barber traps distributed in different ecological contexts of the island. This first post-eradication study reveals an increase in the abundance of arthropods trapped between 2011 (4868 individuals in 74 traps) and 2013 (6892, n = 60). The average number of trapped Arthropods was significantly higher in areas where Carpobrotus spp. have been eradicated, but declined in the bush area that housed a high density of R. rattus. The communities of decomposers explode, in contrast to predator populations. However, the global specific richness remains stable (220 morphospecies in 2011, 216 in 2013). Scientific monitoring by the PNC must be continued to better determine the direct and indirect long-term impacts of these eradications upon the structure and the functioning of the Arthropods communities of the Bagaud Island

PCM4EU and PRIME-ROSE:Collaboration for implementation of precision cancer medicine in Europe

Background: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. Patients and methods: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. Results: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu. eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. Conclusion: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.</p

PCM4EU and PRIME-ROSE:Collaboration for implementation of precision cancer medicine in Europe

Background: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. Patients and methods: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. Results: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu. eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. Conclusion: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.</p

Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease

Amyloid β-peptide (Aβ) is directly linked to Alzheimer's disease (AD). In its monomeric form, Aβ aggregates to produce fibrils and a range of oligomers, the latter being the most neurotoxic. Dysregulation of Ca2+ homeostasis in aging brains and in neurodegenerative disorders plays a crucial role in numerous processes and contributes to cell dysfunction and death. Here we postulated that calcium may enable or accelerate the aggregation of Aβ. We compared the aggregation pattern of Aβ(1–40) and that of Aβ(1–40)E22G, an amyloid peptide carrying the Arctic mutation that causes early onset of the disease. We found that in the presence of Ca2+, Aβ(1–40) preferentially formed oligomers similar to those formed by Aβ(1–40)E22G with or without added Ca2+, whereas in the absence of added Ca2+ the Aβ(1–40) aggregated to form fibrils. Morphological similarities of the oligomers were confirmed by contact mode atomic force microscopy imaging. The distribution of oligomeric and fibrillar species in different samples was detected by gel electrophoresis and Western blot analysis, the results of which were further supported by thioflavin T fluorescence experiments. In the samples without Ca2+, Fourier transform infrared spectroscopy revealed conversion of oligomers from an anti-parallel β-sheet to the parallel β-sheet conformation characteristic of fibrils. Overall, these results led us to conclude that calcium ions stimulate the formation of oligomers of Aβ(1–40), that have been implicated in the pathogenesis of AD

Assessing changes in global fire regimes

PAGES, Past Global Changes, is funded by the Swiss Academy of Sciences and the Chinese Academy of Sciences and supported in kind by the University of Bern, Switzerland. Financial support was provided by the U.S. National Science Foundation award numbers 1916565, EAR-2011439, and EAR-2012123. Additional support was provided by the Utah Department of Natural Resources Watershed Restoration Initiative. SSS was supported by Brigham Young University Graduate Studies. MS was supported by National Science Centre, Poland (grant no. 2018/31/B/ST10/02498 and 2021/41/B/ST10/00060). JCA was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 101026211. PF contributed within the framework of the FCT-funded project no. UIDB/04033/2020. SGAF acknowledges support from Trond Mohn Stiftelse (TMS) and University of Bergen for the startup grant ‘TMS2022STG03’. JMP participation in this research was supported by the Forest Research Centre, a research unit funded by Fundação para a Ciência e a Tecnologia I.P. (FCT), Portugal (UIDB/00239/2020). A.-LD acknowledge PAGES, PICS CNRS 06484 project, CNRS-INSU, Région Nouvelle-Aquitaine, University of Bordeaux DRI and INQUA for workshop support.Background The global human footprint has fundamentally altered wildfire regimes, creating serious consequences for human health, biodiversity, and climate. However, it remains difficult to project how long-term interactions among land use, management, and climate change will affect fire behavior, representing a key knowledge gap for sustainable management. We used expert assessment to combine opinions about past and future fire regimes from 99 wildfire researchers. We asked for quantitative and qualitative assessments of the frequency, type, and implications of fire regime change from the beginning of the Holocene through the year 2300. Results Respondents indicated some direct human influence on wildfire since at least ~ 12,000 years BP, though natural climate variability remained the dominant driver of fire regime change until around 5,000 years BP, for most study regions. Responses suggested a ten-fold increase in the frequency of fire regime change during the last 250 years compared with the rest of the Holocene, corresponding first with the intensification and extensification of land use and later with anthropogenic climate change. Looking to the future, fire regimes were predicted to intensify, with increases in frequency, severity, and size in all biomes except grassland ecosystems. Fire regimes showed different climate sensitivities across biomes, but the likelihood of fire regime change increased with higher warming scenarios for all biomes. Biodiversity, carbon storage, and other ecosystem services were predicted to decrease for most biomes under higher emission scenarios. We present recommendations for adaptation and mitigation under emerging fire regimes, while recognizing that management options are constrained under higher emission scenarios. Conclusion The influence of humans on wildfire regimes has increased over the last two centuries. The perspective gained from past fires should be considered in land and fire management strategies, but novel fire behavior is likely given the unprecedented human disruption of plant communities, climate, and other factors. Future fire regimes are likely to degrade key ecosystem services, unless climate change is aggressively mitigated. Expert assessment complements empirical data and modeling, providing a broader perspective of fire science to inform decision making and future research priorities.Peer reviewe

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio