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Objectives: It is unclear whether recurrent sputum culture with Pseudomonas aeruginosa from patients with chronic obstructive pulmonary disease (COPD) is caused by intermittent airway carriage by different P. aeruginosa lineages or persistent carriage by the same lineage, and whether lineages genetically adapt during carriage. Methods: Whole-genome sequencing was performed for P. aeruginosa isolates sampled longitudinally from sputum cultures in patients with COPD who were enrolled in an ongoing randomized controlled trial (clinicaltrials.gov: NCT03262142). Results: A total of 153 P. aeruginosa isolates were sequenced for 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 patients (83%) and was caused by persistence of the same clonal lineage in all but one patient. We identified 38 genes mutated in parallel in two or more lineages, suggesting positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important in antibiotic resistance and chronic infections to be more frequently mutated. Discussion: Recurrent P. aeruginosa was common and carried for a prolonged time after initial detection in the airways of patients with COPD. Recurrence was caused by persistence of the same clonal lineage and was associated with genetic adaptation. Trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in COPD are warranted.

The aim of this study was to evaluate the effect of exposure to manganese (Mn) on fine motor functions. A total of 48 welders and 30 unexposed workers as controls completed questionnaires, underwent blood examinations, and a motor test battery. The shift exposure of welders to respirable Mn was measured with personal samplers. For all subjects accumulations of Mn in the brain were assessed with T1-weighted magnetic resonance imaging. Welders showed normal motor functions on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale part III. Furthermore welders performed excellent on a steadiness test, showing better results than controls. However, welders were slightly slower than controls in motor tests. There was no association between fine motor test results and the relaxation rates R1 in globus pallidus and substantia nigra as MRI-based biomarkers to quantify Mn deposition in the brain.

Apicomplexan parasites contain rhoptries, which are specialized secretory organelles that coordinate host cell invasion. During the process of invasion, rhoptries secrete their contents to facilitate interaction with, and entry into, the host cell. Here we report the crystal structure of the rhoptry protein A rmadillo R epeats- O nly (ARO) from the human malaria parasite, Plasmodium falciparum (PfARO). The structure of PfARO is comprised of five tandem Armadillo-like (ARM) repeats, with adjacent ARM repeats stacked in a head-to-tail orientation resulting in PfARO adopting an elongated curved shape. Interestingly, the concave face of PfARO contains two distinct patches of highly conserved residues that appear to play an important role in protein-protein interaction. We functionally characterized the P. falciparum homologue of A RO i nteracting p rotein (PfAIP) and demonstrate that it localizes to the rhoptries. We show that conditional mislocalization of PfAIP leads to deficient red blood cell invasion. Guided by the structure, we identified mutations of PfARO that lead to mislocalization of PfAIP. Using proximity-based biotinylation we probe into PfAIP interacting proteins.

Purpose: Lunocapitate arthrodesis is a motion-preserving salvage procedure for painful wrist osteoarthritis. Because the arthrodesis is limited to the capitate and the lunate, the adaptive motion of the triquetrum is theoretically maintained. We aimed to examine whether triquetral motion is sustained in vivo after lunocapitate arthrodesis. Methods: We examined 7 patients after lunocapitate arthrodesis at least 1 year earlier, with computed tomography at 2 wrist positions: maximal radial extension and maximal ulnar flexion. Triquetral motion in vivo was analyzed using volume registration technique of the paired computed tomography scans and compared with the contralateral side. Results: The triquetrum moved in all patients, but the degree of motion was small compared with the nonsurgical wrist. A minor degree of motion of the hamate relative to the fused lunocapitate could also be demonstrated. Conclusions: Triquetral motion is limited after lunocapitate arthrodesis. Type of study/level of evidence: Therapeutic IV. Key words: lunatocapitate arthrodesis, osteoarthritis, scapholunate advanced collapse, scaphoid nonunion advanced collapse, triquetrum

Unilateral neglect is a common cognitive syndrome after stroke, which is defined as a spatially specific unawareness of the contralesional space. The syndrome is caused by disruptions of attentional networks in the brain, which impair the patients' ability to direct attention towards the contralesional space. During recovery, patients often learn to compensate by voluntarily directing their attention to the neglected side at the expense of cognitive resources. In this study, we examined the impact of the complexity of visual input on free visual exploration behavior of unilateral neglect and apparently recovered patients. We asked whether increasing scene complexity would allow the detection of residual unilateral neglect in recovered patients by increasing the amount of cognitive resources needed for visual processing and limiting capacities for compensation. Using virtual reality, we analyzed the spatial distribution of gaze of unilateral neglect patients, patients who had, according to conventional diagnostics, recovered from the syndrome, stroke patients with no history of unilateral neglect, and age-matched healthy controls. We manipulated the complexity of an immersive virtual scene presented on head mounted displays. We identified the orientation bias towards the ipsilesional side as a sensitive and specific marker of unilateral neglect, which was present in unilateral neglect and recovered patients but absent in stroke patients with no history of unilateral neglect and controls. Increasing scene complexity exacerbated the orientation shift in unilateral neglect patients and revealed that three out of nine (33%) recovered patients had a high probability of suffering from residual unilateral neglect as estimated by a generalized linear model using the median horizontal gaze position as a predictor.

Le pharmacien joue un role cle, aupres du medecin traitant, dans le parcours de soins des patients. Les organisations dediees a la coordination des soins different en fonction de la taille du territoire, du nombre de professionnels impliques, de l’envie de se structurer ou non et des evolutions legislatives.

Resume Reseau citoyen d’observateurs des plantes a pollen allergisant, Pollin’air a pour objectif de permettre aux personnes allergiques d’etre prevenues de l’emission des pollens allergisants en temps reel et de maniere geolocalisee. Il a ete initie en juillet 2016 grâce au partenariat entre Air Lorraine (Atmo Grand Est depuis 2017), l’Observatoire regional de la sante et des affaires sociales en Lorraine (ORS Grand Est depuis 2018), le laboratoire d’hydrologie et climatologie medicales de la faculte de medecine de Nancy, le jardin botanique Jean-Marie Pelt (Villers-les-Nancy), l’Agence regionale de sante de Lorraine (desormais ARS Grand Est), l’Union regionale des professionnels de sante pharmaciens de Lorraine (desormais URPS pharmaciens Grand Est) et la Metropole du Grand Nancy. Pollin’air est un reseau participatif qui met en relation des sentinelles benevoles qui observent la pollinisation des especes vegetales a risque allergique et les personnes allergiques, via une plateforme numerique. Grâce aux informations fournies par les premiers, les secondes peuvent adapter leurs comportements de maniere precoce et reduire les effets sanitaires lies aux periodes de pollinisation. Les professionnels de sante peuvent ajuster leurs strategies diagnostiques et therapeutiques. L’observation phenologique de 25 especes allergisantes (floraison, pollinisation, fin de pollinisation) est realisee par les sentinelles des pollens sur le territoire lorrain, les informations sont collectees, en temps reel et de maniere geolocalisee, sur le site www.pollinair.fr sur une carte interactive. Les personnes allergiques peuvent recevoir des alertes personnalisees en fonction de leur allergie et de leur localisation geographique. Pollin’air permet d’acquerir des donnees phenologiques a grande echelle. Il apporte une information qualitative specifique de l’espece vegetale et geolocalisee. D’importantes variations geographiques de pollinisation sont mises en evidence sur le territoire allant jusqu’a 1 mois pour l’armoise. L’analyse des dates de diffusion de l’information pollinique relevees par les 3 outils de surveillance utilises a Nancy montre que veille phenologique realisee au jardin botanique donne l’information la plus precoce 6 fois sur 14, le reseau Pollin’air dans 5 cas et le Reseau national de surveillance aerobiologique (RNSA) dans 3 cas Les enquetes de satisfaction realisees aupres des sentinelles et des personnes allergiques montrent l’acquisition de connaissances tant en botanique que sur les allergies par les participants, l’adhesion de 9 personnes allergiques sur 10 a la proposition d’adapter leur comportement et leur traitement a l’actualite pollinique. Ce reseau participatif a permis de creer une dynamique collective et intergenerationnelle autour de l’enjeu de sante publique que constitue l’allergie aux pollens, en federant professionnels de sante, botanistes, experts de l’air, collectivites et citoyens.

Despite the importance of phosphorus (P) for organisms, the contributions of different processes delivering P into the bioavailable pool in soil have not yet been unraveled mainly due to methodological constraints in separating physico-/geochemical from biological processes. Stable O isotope analyses of phosphate might help to disentangle these processes and recent method improvements now allow an application in terrestrial ecosystems. Plant diversity influences not only plant P uptake but also biological P release mechanisms in soil thereby potentially affecting stable isotope ratios of bioavailable P (δ18OPi). We calculated the degree of enzyme-mediated O incorporation into phosphate, determined the contributions of different biological processes (Pi mobilization from soil organic matter, microbial P turnover), and tested for plant diversity effects on δ18O values of phosphate and of soil water as well as on the processes involved in O incorporation. We added 18O-enriched and 18O-depleted water to separated subplots of 27 study sites differing in plant species richness and plant functional group composition. δ18O values of phosphate and soil water were measured before and six days after labeling. We calculated mixing models based on isotope fractionation published so far. The O incorporation factor a reflecting the proportional incorporation of O atoms from labeled water into phosphate molecules under field conditions averaged 0.33 (0.15–0.70). δ18O values of bioavailable phosphate indicated microbial P processing i.e., turnover and subsequent release of P in soil. Plant species richness was related to δ18O values of soil water via evaporation. Because of the complete exchange of O atoms in a phosphate molecule with ambient water during microbial P turnover in soil, plant species richness effects were also visible in δ18O values of bioavailable phosphate. In conclusion, our approach yielded new insights into the role of microorganisms in supplying bioavailable P. For the first time we could show that plant-community induced microclimate shapes δ18O values of bioavailable phosphate in soil indirectly by affecting δ18O values of soil water with which phosphate exchanges O. Therefore, stable O isotope analyses in phosphate represent a useful tool for unraveling complex plant-soil-microorganism interactions in the P cycle.

JBC 298(9), 102360 (2022). doi:10.1016/j.jbc.2022.102360, Malaria is responsible for hundreds of thousands of deaths every year. The lack of an effective vaccine and the global spread of multidrug resistant parasites hampers the fight against the disease and underlines the need for new antimalarial drugs. Central to the pathogenesis of malaria is the proliferation of Plasmodium parasites within human erythrocytes. Parasites invade erythrocytes via a coordinated sequence of receptor–ligand interactions between the parasite and the host cell. Posttranslational modifications such as protein phosphorylation are known to be key regulators in this process and are mediated by protein kinases. For several parasite kinases, including the Plasmodium falciparum glycogen synthase kinase 3 (PfGSK3), inhibitors have been shown to block erythrocyte invasion. Here, we provide an assessment of PfGSK3 function by reverse genetics. Using targeted gene disruption, we show the active gene copy, PfGSK3β, is not essential for asexual blood stage proliferation, although it modulates efficient erythrocyte invasion. We found functional inactivation leads to a 69% decreased growth rate and confirmed this growth defect by rescue experiments with wildtype and catalytically inactive mutants. Functional knockout of PfGSK3β does not lead to transcriptional upregulation of the second copy of PfGSK3. We further analyze expression, localization, and function of PfGSK3β during gametocytogenesis using a parasite line allowing conditional induction of sexual commitment. We demonstrate PfGSK3β-deficient gametocytes show a strikingly malformed morphology leading to the death of parasites in later stages of gametocyte development. Taken together, these findings are important for our understanding and the development of PfGSK3 as an antimalarial target., Published by American Soc. for Biochemistry and Molecular Biology, Bethesda, MD.

Objective Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. Material and methods GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson’s disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only). Results The median shift exposure to respirable Mn and Fe in active welders was 23 μg/m3 and 110 μg/m3, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(β) = 0.87, p Conclusions Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.

Many floodplain soils worldwide are contaminated by present and past industrial and mining activities. During flooding redox potential decreases, triggering the release of dissolved and colloidal metals. We used an anaerobic microcosm incubation to simulate flooding of a carbonate-rich floodplain soil for 40 days. Soil solution samples were extracted to determine the release of dissolved (< 0.02 μm) and colloidal fractions (0.02–10 μm). We analyzed stable isotope ratios of colloidal and dissolved Fe and Cu representing two groups of metals with different release behavior; release of Fe was steadily increasing, while that of Cu peaked sharply after flooding and decreased afterwards. The temporal trend of δ56Fe values of total Fe in solution indicated dissimilatory iron reduction. The apparent isotopic fractionation between dissolved and colloidal Fe (Δ56Fedissolved-colloidal = δ56Fedissolved − δ56Fecolloidal) varied from 0.31 ± 0.04‰ to − 1.86 ± 0.26‰. Low δ56Fecolloidal (− 1.16 ± 0.04‰) values on day 4 of the experiment suggested colloid formation by precipitation of dissolved Fe, while the strong temporal variation in Δ56Fedissolved-colloidal indicated subsequent changes in colloid mineralogy, sorption to soil components and/or electron transfer-atom exchange. The variations in δ65Cu values (Δ65Cudissolved-colloidal from 0.81 ± 0.03‰ to 1.58 ± 0.09‰) are probably linked to the changing oxidation state of colloidal Cu. While at the beginning of the experiment colloidal Cu and solid soil Cu exchange, these systems decouple after the onset of sulfate reduction in the second half of the experiment. The experimental results fit well to findings from redoximorphic soils described in the literature and highlight the importance of colloids for metal release and the isotopic pattern in carbonatic soils.

Diffusion MRI (dMRI) provides rich information on the white matter of the human brain, enabling insight into neurological disease, normal aging, and neuroplasticity. We present BundleMAP, an approach to extracting features from dMRI data that can be used for supervised classification, regression, and hypothesis testing. Our features are based on aggregating measurements along nerve fiber bundles, enabling visualization and anatomical interpretation. The main idea behind BundleMAP is to use the ISOMAP manifold learning technique to jointly parametrize nerve fiber bundles. We combine this idea with mechanisms for outlier removal and feature selection to obtain a practical machine learning pipeline. We demonstrate that it increases accuracy of disease detection and estimation of disease activity, and that it improves the power of statistical tests.

Growth limitation induced by Al toxicity is believed to commonly occur in tropical forests, although a direct proof is frequently lacking. To test for the general assumption of Al toxicity, Al, Ca, and Mg concentrations in precipitation, throughfall, stemflow, organic layer leachate, mineral soil solutions, stream water, and the leaves of 17 native tree species were analyzed. We calculated Al fluxes and modeled Al speciation in the litter leachate and mineral soil solutions. We assessed potential Al toxicity based on soil base saturation, Al concentrations, Ca:Al and Mg:Al molar ratios and Al speciation in soil solution as well as Al concentrations and Ca:Al and Mg:Al molar ratios in tree leaves. High Al fluxes in litterfall (8.77 ± 1.3 to 14.2 ± 1.9 kg ha− 1 yr− 1, mean ± SE) indicated a high Al circulation through the ecosystem. The fraction of exchangeable and potentially plant-available Al in mineral soils was high, being a likely reason for a low root length density in the mineral soil. However, Al concentrations in all solutions were consistently below critical values and Ca:Al molar and the Ca2 +:Alinorganic molar ratios in the organic layer leachate and soil solutions were above 1, the suggested threshold for Al toxicity. Except for two Al-accumulating and one non-accumulating tree species, the Ca:Al molar ratios in tree leaves were above the Al toxicity threshold of 12.5. Our results demonstrate high Al cycling through the vegetation partly because of the presence of some Al accumulator plants. However, there was little indication of an Al toxicity risk in soil and of acute Al toxicity in plants likely reflecting that tree species are well adapted to the environmental conditions at our study site and thus hardly prone to Al toxicity.

Marine Isotope Stage 3 is considered a period with several climate oscillations that drove the environments to rapid changes. To understand how these stadial-interstadial cycles affected southern Poland, we combined the results of eight proxies analysed in the samples from the old excavations and a new 2017 trench of Koziarnia Cave (Ojcow National Park, Krakow-Czestochowa Upland, Poland) in layers related to Middle Palaeolithic, Jerzmanowician, and Early Gravettian. Among the studied proxies were charcoals, pollen record, remains of malacofauna, and vertebrates (including rodents, birds and large mammals, and ZooMS analysis of fragmented bones). Moreover, sediment samples have been analysed for lipid composition (by Gas Chromatography-Mass Spectrometry, GC–MS). Despite several taphonomic issues, it was possible to recognise two oscillations. The first one, reflected in pollen record and lipid analysis, took place during Dansgaard-Oeschger (DO) 14 to 8 and included Heinrich Stadial (HS) 4. The second one, recorded by rodents and bird proxies, was related to DO 8/7 to DO 6 and included HS 3. Charcoal and large mammal proxies provided the broad context of our study. The Jerzmanowician occupation was connected with a relatively cold episode in a landscape characterized mainly by grassland and periglacial environments, while the Late Middle Palaeolithic and Early Gravettian groups settled the cave during milder climatic conditions, where environments were open with sparse boreal woodlands. Such trends provide additional arguments in a broad discussion on Middle-Upper Palaeolithic transition in Central Europe.

Purpose Systemic lupus erythematosus (SLE) is a predominantly female autoimmune disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25–70% of SLE patients. Using diffusion tensor imaging, various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate if changes can be detected in the individual white matter tracts in SLE patients regardless if neuropsychiatric symptoms are present or not. Materials and Methods Magnetic resonance diffusion tractography in several individual white matter tracts that are involved in language and memory tasks, including tracts to cortical association areas, was applied in 21 patients with NPSLE (mean age: 40.7 ± 12.8 years; range: 22–67 years), 18 patients with non-neurologic systemic lupus erythematosus (non-NPSLE) (mean age: 40.6 ± 12 years; range: 22–67 years), and 20 healthy control (HC) individuals (mean age: 40.64 ± 12.7 years; range: 19–60 years). Additional patients were evaluated; however, because of the inability to complete the scans required, they were excluded from the study. The fractional anisotropy of individual fiber tracts was measured and correlated with cognitive function and lupus disease severity index (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]) to assess predictability and diagnostic value of these measures for NPSLE. Results Analyses of variance of the tractography data from the analysis of 21 tracts revealed decreased fractional anisotropy in uncinate fasciculus in the NPSLE patients when compared to non-NPSLE lupus patients and HC individuals (P = 0.002). Non-NPSLE patients also demonstrated decreased fractional anisotropy when compared to healthy patients (P = 0.03). Decreased fractional anisotropy was also identified in the corpus callosum and corona radiata in NPSLE patients when compared to HC individuals; however, these tracts did not show a significant difference between NPSLE and non-NPSLE patients. Decreased fractional anisotropy in the uncinate fasciculus correlated with low SLEDAI score (R2 = 0.32). Conclusions Diffusion tensor tractography corroborates findings of decreased white matter integrity within the anterior corona radiate as well as the corpus callosum as previously described. Specifically, our study identified changes in the uncinate fasciculus in NPSLE and non-NPSLE patients that correlate with clinical changes (SLEDAI scores) and are independent of conventional T2 lesion burden. (Less)

Europe is one of the world’s largest food producers, and climate change may pose a serious threat to food security in the region. In the present study, we assess the potential impact of climate change on the Colorado Potato Beetle (CPB), Leptinotarsa decemlineata (Say)—a severe pest of potato (Solanum tuberosum, L.). We also investigate the possible impact of climate change on the phenological development of potato. The main focus is on factors that may limit the northward expansion of the CPB, and the number of generations per year in areas where the insect pest is already present. These factors include lack of temperature sum for completed development before winter, and lack of food (i.e. potato) due to mismatches in insect-host plant phenological synchrony. We use a gridded observational dataset and an ensemble of bias corrected regional climate model data for the period of 1981–2099, representing RCP8.5, as input to a potato and CPB phenological model. The results show that in the future, CPB individuals with a low developmental threshold (+10 °C) can complete maturity of two generations per year before potato is harvested in most parts of Europe. A third generation of CPB may not be able to complete maturation due to lack of food in south and central Europe, while temperature becomes a limiting factor further north. In north-eastern Europe, the initiation of a first generation may be delayed due to lack of food in spring. CPBs with a high developmental threshold (+12 °C) will emerge later from winter hibernation, and food availability will therefore not be a problem in spring. However, individuals with a high developmental threshold face a greater risk of regeneration failure caused by harvesting of potato in autumn. The potential lack of food in autumn may also increase the strength of selection towards a low developmental threshold in northern populations. The combined analysis of CPB and potato phenology indicated that climate change can lead to increased pressure from the CPB in most potato growing areas.

In climate change research ensembles of climate simulations are produced in an attempt to cover the uncertainty in future projections. Many climate change impact studies face difficulties using the full number of simulations available, and therefore often only subsets are used. Until now such subsets were chosen based on their representation of temperature change or by accessibility of the simulations. By using more specific information about the needs of the impact study as guidance for the clustering of simulations, the subset fits the purpose of climate change impact research more appropriately. Here, the sensitivity of such a procedure is explored, particularly with regard to the use of different climate variables, seasons, and regions in Europe. While temperature dominates the clustering, the resulting selection is influenced by all variables, leading to the conclusion that different subsets fit different impact studies best. Display Omitted We present a method to reduce ensembles of climate models.We use hierarchical clustering, SVD, Silhouettes and mean distances.To minimise the information loss the selection is fitted to the data application.The method shows strong sensitivity to the choice of variables/information provided.Strong need for a careful and thoughtful selection process is shown.