Search

Abstract The anthrax-causing bacterium Bacillus anthracis comprises the genetic clades A, B, and C. In the northernmost part (Pafuri) of Kruger National Park (KNP), South Africa, both the common A and rare B strains clades occur. The B clade strains were reported to be dominant in Pafuri before 1991, while A clade strains occurred towards the central parts of KNP. The prevalence of B clade strains is currently much lower as only A clade strains have been isolated from 1992 onwards in KNP. In this study 319 B. anthracis strains were characterized with 31-loci multiple-locus variable-number tandem repeat analysis (MLVA-31). B clade strains from soil (n = 9) and a Tragelaphus strepsiceros carcass (n = 1) were further characterised by whole genome sequencing and compared to publicly available genomes. The KNP strains clustered in the B clade before 1991 into two dominant genotypes. South African strains cluster into a dominant genotype A.Br.005/006 consisting of KNP as well as the other anthrax endemic region, Northern Cape Province (NCP), South Africa. A few A.Br.001/002 strains from both endemic areas were also identified. Subclade A.Br.101 belonging to the A.Br.Aust94 lineage was reported in the NCP. The B-clade strains seems to be vanishing, while outbreaks in South Africa are caused mainly by the A.Br.005/006 genotypes as well as a few minor clades such as A.Br.001/002 and A.Br.101 present in NCP. This work confirmed the existence of the rare and vanishing B-clade strains that group in B.Br.001 branch with KrugerB and A0991 KNP strains.

Abstract $$^{177}{\hbox {Lu}}$$ 177 Lu radiopharmaceutical therapy is a standardized systemic treatment, with a typical dose of 7.4 GBq per injection, but its response varies from patient to patient. Dosimetry provides the opportunity to personalize treatment, but it requires multiple post-injection images to monitor the radiopharmaceutical’s biodistribution over time. This imposes an additional imaging burden on centers with limited resources. This review explores methods to lessen this burden by optimizing acquisition types and minimizing the number and duration of imaging sessions. After summarizing the different steps of dosimetry and providing examples of dosimetric workflows for $$^{177}{\hbox {Lu}}$$ 177 Lu -DOTATATE and $$^{177}{\hbox {Lu}}$$ 177 Lu -PSMA, we examine dosimetric workflows based on a reduced number of acquisitions, or even just one. We provide a non-exhaustive description of simplified methods and their assumptions, as well as their limitations. Next, we detail the specificities of each normal tissue and tumors, before reviewing dose-response relationships in the literature. In conclusion, we will discuss the current limitations of dosimetric workflows and propose avenues for improvement.

Abstract Anaesthetics are used daily in human and veterinary medicine as well as in scientific research. Anaesthetics have an impact on cell homeostasis especially through modulation of protein post-translational modifications. O-GlcNAcylation, a ubiquitous post-translational modification, plays a role in many biological processes. The aims of this study were to evaluate whether (1) anaesthesia influences O-GlcNAcylation and (2) its stimulation affects physiological parameters. Male Wistar rats (n = 38) were anaesthetized with ketamine-xylazine or isoflurane. They randomly received either an intravenous injection of Ringer's lactate or NButGT (10mg/kg) in order to increase O-GlcNAcylation levels. One hour after induction of anaesthesia, haemodynamic parameters and plasmatic markers were evaluated. Heart, brain and lungs were harvested and O-GlcNAcylation levels and O-GlcNAc-related enzymes were evaluated by western blot. Cardiac and pulmonary O-GlcNAcylation levels and cardiac, cerebral and pulmonary O-GlcNAc associated enzyme expression were not impacted with anaesthesia. Compared with ketamine-xylazine, isoflurane had a lower impact on blood pressure, heart rate and glycaemia. Pharmacological stimulation of O-GlcNAcylation by NButGT did not affect the physiological parameters. This study offers unprecedented insights into the regulation of O-GlcNAcylation and O-GlcNAc related enzymes during anaesthesia. Pharmacological stimulation of O-GlcNAcylation over a 1-h period did not disrupt the physiological balance in healthy anaesthetized rats.

In semi-arid areas, groundwater (GW) represents the most reliable resource for water supply. In the semi-arid region of Ceará (Northeastern Brazil), GW of the crystalline fractured aquifers has a salinity higher than expected in this type of environment. This study implemented a multidisciplinary approach based on hydrodynamic (piezometric) and hydrogeochemical (18O, 2H, 3H, 14C, CFC, SF6, Electrical Conductivity, major ions) data to understand the salinization processes. Results demonstrate that GW is generally recent and recharged by meteoric waters mainly through indirect infiltration from evaporated surface water. The study suggests that GW, originally bicarbonated, becomes progressively enriched in chloride due to the dissolution and leaching of salts, during the wet season, which come from meteoric inputs and have precipitated in the unsaturated zone and pond sediments during dryer periods.

Societal Impact Statement Various techniques to modify genomes have been developed over the past decades, from molecular cloning to gene editing techniques. What are their applications? What are the key themes discussed by scientists? To answer these questions, we provide a qualitative and quantitative analysis of 14,739 scientific articles published between 1990 to 2022 showing that some themes are constant over time, such as the molecular aspects of genetics and discussions about data and software, while other themes emerged more recently. For example, CRISPR/Cas9 became prominent from 2012 onwards, and applications in agriculture and policy/regulatory implications from 2015 onwards. This mixed method opens up new spaces for dialogue between the natural and social sciences and captures the shifting boundaries of science. Summary The article analyzes publications in the biological sciences concerned with genetic engineering, in particular gene editing, between 1990 and 2022 to examine key and emerging themes. It provides a lexicometric analysis of 14,739 articles, which were subdivided into four periods (1990–2011, 2012–2015, 2016–2018, and 2019–2022). We show that certain themes are constant over time, such as the molecular aspects of genetic engineering techniques and discussions about data and software. Other themes, however, have emerged at specific moments in time: CRISPR/Cas9 became prominent from 2012 onwards and applications in agriculture and policy and regulatory implications from 2015 onwards. We observe, in particular, a semantic shift from genetically modified organisms (GMOs) to crops. The article contributes to debates about the boundaries of science by shedding light on the temporal dynamics of boundary‐work and by showing how the frames of scientific debates can shift to account for the political aspects of science. We conclude that the dialogue between the natural and social sciences can be strengthened by showing that apart from scientometric approaches, there are other methods to analyze “what counts” in science.

Background: Dietary intake and metabolism variations are associated with molecular changes and more particularly in the transcriptome. O-GlcNAcylation is a post-translational modification added and removed respectively by OGT and OGA. The UDP-GlcNAc, the substrate of OGT, is produced by UAP1 and UAP1L1. O-GlcNAcylation is qualified as a metabolic sensor and is involved in the modulation of gene expression. We wanted to unveil if O-GlcNAcylation is linking metabolic transition to transcriptomic changes and to highlight modifications of O-GlcNAcylation during the postnatal cardiac development. Methods: Hearts were harvested from rats at birth (D0), before (D12) and after suckling to weaning transition with normal (D28) or delayed weaning diet from D12 to D28 (D28F). O-GlcNAcylation levels and proteins expression were evaluated by Western blot. Cardiac transcriptomes were evaluated via 3′SRP analysis. Results: Cardiac O-GlcNAcylation levels and nucleocytoplasmic OGT (ncOGT) were decreased at D28 while full length OGA (OGA) was increased. O-GlcNAcylation levels did not changed with delayed weaning diet while ncOGT and OGA were respectively increased and decreased. Uapl1 was the only O-GlcNAcylation-related gene identified as differentially expressed throughout postnatal development. Conclusion: Macronutrients switch promotes changes in the transcriptome landscape that are independent from O-GlcNAcylation levels. UAP1 and UAP1L1 are not the main regulator element of O-GlcNAcylation throughout postnatal development.

After reports in 2017 of Brucella neotomae infections among humans in Costa Rica, we sequenced 12 strains isolated from rodents during 1955–1964 from Utah, USA. We observed an exact strain match between the human isolates and 1 Utah isolate. Independent confirmation is required to clarify B. neotomae zoonotic potential.

The dataset proposed is a collection of pedestrian navigation data sequences combining visual and spatial information. The pedestrian navigation sequences are situations encountered by a pedestrian walking in an urban outdoor environment, such as moving on the sidewalk, navigating through a crowd, or crossing a street when the pedestrian light traffic is green. The acquired data are timestamped provided RGB-D images and are associated with GPS, and inertial data (acceleration, rotation). These recordings were acquired by separate processes, avoiding delays during their capture to guarantee a synchronisation between the moment of acquisition by the sensor and the moment of recording on the system. The acquisition was made in the city of Dijon, France, including narrow streets, wide avenues, and parks.Annotations of the RGB-D are also provided by bounding boxes indicating the position of relevant static or dynamic objects present in a pedestrian area, such as a tree, bench, or person. This pedestrian navigation dataset aims to support the development of smart mobile systems to assist visually impaired people in their daily movements in an outdoor environment. In this context, the visual data and localisation sequences we provide can be used to elaborate the appropriate visual processing methods to extract relevant information about the obstacles and their current positions on the path. Alongside the dataset, a visual-to-auditory substitution method has been employed to convert each image sequence into corresponding stereophonic sound files, allowing for comparison and evaluation. Synthetic sequences associated with the same information set are also provided based on the recordings of a displacement within the 3D model of a real place in Dijon.

Abstract Background The aim of this study was to investigate the quantification performance of a 360° CZT camera for 177Lu-based treatment monitoring. Methods Three phantoms with known 177Lu activity concentrations were acquired: (1) a uniform cylindrical phantom for calibration, (2) a NEMA IEC body phantom for analysis of different-sized spheres to optimise quantification parameters and (3) a phantom containing two large vials simulating organs at risk for tests. Four sets of reconstruction parameters were tested: (1) Scatter, (2) Scatter and Point Spread Function Recovery (PSFR), (3) PSFR only and (4) Penalised likelihood option and Scatter, varying the number of updates (iterations × subsets) with CT-based attenuation correction only. For each, activity concentration (ARC) and contrast recovery coefficients (CRC) were estimated as well as root mean square. Visualisation and quantification parameters were applied to reconstructed patient image data. Results Optimised quantification parameters were determined to be: CT-based attenuation correction, scatter correction, 12 iterations, 8 subsets and no filter. ARC, CRC and RMS results were dependant on the methodology used for calculations. Two different reconstruction parameters were recommended for visualisation and for quantification. 3D whole-body SPECT images were acquired and reconstructed for 177Lu-PSMA patients in 2–3 times faster than the time taken for a conventional gamma camera. Conclusion Quantification of whole-body 3D images of patients treated with 177Lu-PSMA is feasible and an optimised set of parameters has been determined. This camera greatly reduces procedure time for whole-body SPECT.

Tularemia is an acute febrile disease caused by the Gram-negative bacillus Francisella tularensis. Based on genetic and phenotypic characteristics, three subspecies are distinguished: tularensis, holarctica, and mediasiatica. F. tularensis subsp. mediasiatica remains the least studied subspecies. Over the past decade, new foci of distribution of F. tularensis subsp. mediasiatica have been discovered in Russia (Siberia), expanding the possible distribution area by thousands of kilometers. This article provides whole genome single nucleotide polymorphism (wgSNP) and polymorphic tandem repeats (MLVA) analyses of 28 mediasiatica strains isolated between 1965 and 2004 in Kazakhstan. Despite high genetic homogeneity, MLVA with eleven loci (MLVA11) demonstrates a high discriminatory ability (diversity index, 0.9497). The topological structure of the trees based on wgSNP and MLVA is not comparable; however, clustering remains congruent for most outbreaks, with the exception of two strains from one outbreak that are identical in terms of wgSNP but differ at three tandem repeat loci. Based on wgSNP, the strains are assigned to one of the three currently known mediasiatica sublineages, lineage M.I, together with other historical strains maintained in collections in Russia and Sweden. wgSNP shows limited previously unknown genetic diversity, with the M.I lineage size being only 118 SNPs. The wgSNP genotype is not strongly correlated with year and place of isolation.

This text reports on the discussions that took place during the 'Transmettre la discipline' workshop held in November 2022 at Université Grenoble Alpes. The purpose of the workshop was to discuss the pedagogy of geography in higher education and to contribute to the gradual structuring of this research field. The workshop was led by Camille Vergnaud and Laura Péaud and was attended by approximately fifteen participants from France and abroad. The event was structured into plenary lectures and feedback workshops, providing an opportunity to discuss the teaching of geography. The attendees specifically analysed the discipline's unique characteristics and their ongoing changes.

Abstract Background In selective internal radiation therapy, 99mTc SPECT images are used to optimize patient treatment planning, but they are affected by respiratory motion. In this study, we evaluated on patient data the dosimetric impact of motion-compensated SPECT reconstruction on several volumes of interest (VOI), on the tumor-to-normal liver (TN) ratio and on the activity to be injected. Methods Twenty-nine patients with liver cancer or hepatic metastases treated by radioembolization were included in this study. The biodistribution of 90Y is assumed to be the same as that of 99mTc when predictive dosimetry is implemented. A total of 31 99mTc SPECT images were acquired and reconstructed with two methods: conventional OSEM (3D) and motion-compensated OSEM (3Dcomp). Seven VOI (liver, lungs, tumors, perfused liver, hepatic reserve, healthy perfused liver and healthy liver) were delineated on the CT or obtained by thresholding SPECT images followed by Boolean operations. Absorbed doses were calculated for each reconstruction using Monte Carlo simulations. Percentages of dose difference (PDD) between 3Dcomp and 3D reconstructions were estimated as well as the relative differences for TN ratio and activities to be injected. The amplitude of movement was determined with local rigid registration of the liver between the 3Dcomp reconstructions of the extreme phases of breathing. Results The mean amplitude of the liver was 9.5 ± 2.7 mm. Medians of PDD were closed to zero for all VOI except for lungs (6.4%) which means that the motion compensation overestimates the absorbed dose to the lungs compared to the 3D reconstruction. The smallest lesions had higher PDD than the largest ones. Between 3D and 3Dcomp reconstructions, means of differences in lung dose and TN ratio were not statistically significant, but in some cases these differences exceed 1 Gy (4/31) and 8% (2/31). The absolute differences in activity were on average 3.1% ± 5.1% and can reach 22.8%. Conclusion The correction of respiratory motion mainly impacts the lung and tumor doses but only for some patients. The largest dose differences are observed for the smallest lesions.

This paper presents a new profiling side-channel attack on CRYSTALSDilithium, the new NIST primary standard for quantum-safe digital signatures. An open source implementation of CRYSTALS-Dilithium is already available, with constant-time property as a consideration for side-channel resilience. However, this implementation does not protect against attacks that exploit intermediate data leakage. We show how to exploit a new leakage on a vector generated during the signing process, for which the costly protection by masking is still a matter of debate. With a corpus of 700 000 messages, we design a template attack that enables us to efficiently predict whether a given coefficient in one coordinate of this vector is zero or not. By gathering signatures and being able to make the correct predictions for each index, and then using linear algebra methods, this paper demonstrates that one can recover part of the secret key that is sufficient to produce universal forgeries. While our paper deeply discusses the theoretical attack path, it also demonstrates the validity of the assumption regarding the required leakage model from practical experiments with the reference implementation on an ARM Cortex-M4. We need approximately a day to collect enough representatives and one more day to perform the traces acquisition on our target.

Abstract We present a comparative investigation of the influence of crystallinity and film thickness on the acoustic and thermal properties of layered PtSe2 films of varying thickness (1–40 layers) using frequency-domain thermo-reflectance, low-frequency Raman, and pump-probe coherent phonon spectroscopy. We find ballistic cross-plane heat transport up to ~30 layers PtSe2 and a 35% reduction in the cross-plane thermal conductivity of polycrystalline films with thickness larger than 20 layers compared to the crystalline films of the same thickness. First-principles calculations further reveal a high degree of thermal conductivity anisotropy and a remarkable large contribution of the optical phonons to the thermal conductivity in bulk (~20%) and thin PtSe2 films (~30%). Moreover, we show strong interlayer interactions in PtSe2, short acoustic phonon lifetimes in the range of picoseconds, an out-of-plane elastic constant of 31.8 GPa, and a layer-dependent group velocity ranging from 1340 ms−1 in bilayer to 1873 ms−1 in eight layers of PtSe2. The potential of tuning the lattice thermal conductivity of layered materials with the level of crystallinity and the real-time observation of coherent phonon dynamics open a new playground for research in 2D thermoelectric devices and provides guidelines for thermal management in 2D electronics.

Abstract Background The number of SPECT/CT time-points is important for accurate patient dose estimation in peptide receptor radionuclide therapy. However, it may be limited by the patient’s health and logistical reasons. Here, an image-based dosimetric workflow adapted to the number of SPECT/CT acquisitions available throughout the treatment cycles was proposed, taking into account patient-specific pharmacokinetics and usable in clinic for all organs at risk. Methods Thirteen patients with neuroendocrine tumors were treated with four injections of 7.4 GBq of $$^{177}$$ 177 Lu-DOTATATE. Three SPECT/CT images were acquired during the first cycle (1H, 24H and 96H or 144H post-injection) and a single acquisition (24H) for following cycles. Absorbed doses were estimated for kidneys (LK and RK), liver (L), spleen (S), and three surrogates of bone marrow (L2 to L4, L1 to L5 and T9 to L5) that were compared. 3D dose rate distributions were computed with Monte Carlo simulations. Voxel dose rates were averaged at the organ level. The obtained Time Dose-Rate Curves (TDRC) were fitted with a tri-exponential model and time-integrated. This method modeled patient-specific uptake and clearance phases observed at cycle 1. Obtained fitting parameters were reused for the following cycles, scaled to the measure organ dose rate at 24H. An alternative methodology was proposed when some acquisitions were missing based on population average TDRC (named STP-Inter). Seven other patients with three SPECT/CT acquisitions at cycles 1 and 4 were included to estimate the uncertainty of the proposed methods. Results Absorbed doses (in Gy) per cycle available were: 3.1 ± 1.1 (LK), 3.4 ± 1.5 (RK), 4.5 ± 2.8 (L), 4.6 ± 1.8 (S), 0.3 ± 0.2 (bone marrow). There was a significant difference between bone marrow surrogates (L2 to L4 and L1 to L5, Wilcoxon’s test: p value < 0.05), and while depicting very doses, all three surrogates were significantly different than dose in background (p value < 0.01). At cycle 1, if the acquisition at 24H is missing and approximated, medians of percentages of dose difference (PDD) compared to the initial tri-exponential function were inferior to 3.3% for all organs. For cycles with one acquisition, the median errors were smaller with a late time-point. For STP-Inter, medians of PDD were inferior to 7.7% for all volumes, but it was shown to depend on the homogeneity of TDRC. Conclusion The proposed workflow allows the estimation of organ doses, including bone marrow, from a variable number of time-points acquisitions for patients treated with $$^{177}$$ 177 Lu-DOTATATE.

Acute kidney injury is one of the most important complications in patients with COVID-19 and is considered a negative prognostic factor with respect to patient survival. The occurrence of direct infection of the kidney by SARS-CoV-2, and its contribution to the renal deterioration process, remain controversial issues. By studying 32 renal biopsies from patients with COVID-19, we verified that the major pathological feature of COVID-19 is acute tubular injury (ATI). Using single-molecule fluorescence in situ hybridization, we showed that SARS-CoV-2 infected living renal cells and that infection, which paralleled renal angiotensin-converting enzyme 2 expression levels, was associated with increased death. Mechanistically, a transcriptomic analysis uncovered specific molecular signatures in SARS-CoV-2–infected kidneys as compared with healthy kidneys and non–COVID-19 ATI kidneys. On the other hand, we demonstrated that SARS-CoV-2 and hantavirus, 2 RNA viruses, activated different genetic networks despite triggering the same pathological lesions. Finally, we identified X-linked inhibitor of apoptosis-associated factor 1 as a critical target of SARS-CoV-2 infection. In conclusion, this study demonstrated that SARS-CoV-2 can directly infect living renal cells and identified specific druggable molecular targets that can potentially aid in the design of novel therapeutic strategies to preserve renal function in patients with COVID-19.

Brucella abortus is the main causative agent of brucellosis in cattle, leading to severe economic consequences in agriculture and affecting public health. The zoonotic nature of the infection increases the need to control the spread and dynamics of outbreaks in animals with the incorporation of high resolution genotyping techniques. Based on such methods, B. abortus is currently divided into three clades, A, B, and C. The latter includes subclades C1 and C2. This study presents the results of whole-genome sequencing of 49 B. abortus strains isolated in Kazakhstan between 1947 and 2015 and of 36 B. abortus strains of various geographic origins isolated from 1940 to 2004. In silico Multiple Locus Sequence Typing (MLST) allowed to assign strains from Kazakhstan to subclades C1 and to a much lower extend C2. Whole-genome Single-Nucleotide Polymorphism (wgSNP) analysis of the 46 strains of subclade C1 with strains of worldwide origins showed clustering with strains from neighboring countries, mostly North Caucasia, Western Russia, but also Siberia, China, and Mongolia. One of the three Kazakhstan strains assigned to subclade C2 matched the B. abortus S19 vaccine strain used in cattle, the other two were genetically close to the 104 M vaccine strain. Bayesian phylodynamic analysis dated the introduction of B. abortus subclade C1 into Kazakhstan to the 19th and early 20th centuries. We discuss this observation in view of the history of population migrations from Russia to the Kazakhstan steppes.

Abstract In recent years, two-dimensional van der Waals materials have emerged as an important platform for the observation of long-range ferromagnetic order in atomically thin layers. Although heterostructures of such materials can be conceived to harness and couple a wide range of magneto-optical and magneto-electrical properties, technologically relevant applications require Curie temperatures at or above room temperature and the ability to grow films over large areas. Here we demonstrate the large-area growth of single-crystal ultrathin films of stoichiometric Fe5GeTe2 on an insulating substrate using molecular beam epitaxy. Magnetic measurements show the persistence of soft ferromagnetism up to room temperature in 12 nm-thick films, with a Curie temperature of 293 K, and a weak out-of-plane magnetocrystalline anisotropy. The ferromagnetic order is preserved in bilayer Fe5GeTe2, with Curie temperature decreasing to 229 K. Surface, chemical, and structural characterizations confirm the layer-by-layer growth, 5:1:2 Fe:Ge:Te stoichiometric elementary composition, and single-crystalline character of the films.

Catheter removal is recommended in adults with Staphylococcus aureus central-line-associated bloodstream infection (CLABSI) but is controversial in children with long-term central venous catheters (LTCVC). We evaluated the occurrence of catheter salvage strategy (CSS) in children with S. aureus LTCVC-associated CLABSI and assessed determinants of CSS failure. We retrospectively included children (<18 years) with an LTCVC and hospitalized with S. aureus CLABSI in eight French tertiary-care hospitals (2010–2018). CSS was defined as an LTCVC left in place ≥72 h after initiating empiric antibiotic treatment for suspected bacteraemia. Characteristics of patients were reviewed, and multi-variable logistic regression was performed to identify factors associated with CSS failure (i.e., persistence, recurrence or complications of bacteraemia). We included 273 episodes of S. aureus LTCVC-associated CLABSI. CSS was chosen in 194 out of 273 (71%) cases and failed in 74 of them (38%). The main type of CSS failure was the persistence of bacteraemia (39 of 74 cases, 53%). Factors independently associated with CSS failure were: history of catheter infection (adjusted odds ratio (aOR) 3.18, 95% confidence interval (CI) 1.38–7.36), CLABSI occurring on an implantable venous access device (aOR 7.61, 95% CI 1.98–29.20) when compared with tunnelled-cuffed CVC, polymicrobial CLABSI (aOR 3.45, 95% CI 1.25–9.50), and severe sepsis at the initial stage of infection (aOR 4.46, 95% CI 1.18–16.82). CSS was frequently chosen in children with S. aureus LTCVC-associated CLABSI, and failure occurred in one-third of cases. The identified risk factors may help clinicians identify children at risk for CSS failure. [ABSTRACT FROM AUTHOR]

Anthrax is a particularly dangerous infection of humans and ungulates caused by the Gram-positive spore-forming bacterium Bacillus anthracis. The highly monomorphic and clonal species B. anthracis is commonly divided into three main lineages, A, B, and C, which in turn are divided into several canSNP groups. We report here a phylogenetic analysis based on the whole-genome sequence (WGS) data of fifteen strains isolated predominantly in Siberia or Central and Southern Russia. We confirm the wide distribution of the cluster of strains of the B.Br.001/002 group, endemic to the Russian Arctic, which is also present in the steppe zone of Southern Siberia. We characterize additional branches within the major A.Br.001/002 polytomy comprising the A.Br.Ames and A.Br.Sterne lineages, one of which is identified in the Arctic.

Multifunctional substitutes for bone tissue engineering have gained significant interest in recent years in the aim to address the clinical challenge of treating large bone defects resulting from surgical procedures. Sol–gel mesoporous bioactive glass nanoparticles (MBGNs) have emerged as a promising solution due to their high reactivity and versatility. The effect of calcium content on MBGNs textural properties is well known. However, the relationship between their composition, textural properties, and reactivity has not yet been thoroughly discussed in existing studies, leading to divergent conclusions. In this study, pristine and copper-doped binary MGBNs were synthesized by a modified Stöber method, using a cationic surfactant as pore-templating agent. An opposite evolution between calcium content (12–26 wt%) and specific surface area (909–208 m2/g) was evidenced, while copper introduction (8.8 wt%) did not strongly affect the textural properties. In vitro bioactivity assessments conducted in simulated body fluid (SBF) revealed that the kinetics of hydroxyapatite (HAp) crystallization are mainly influenced by the specific surface area, while the composition primarily controls the quantity of calcium phosphate produced. The MBGNs exhibited a good bioactivity within 3 h, while Cu-MBGNs showed HAp crystallization after 48 h, along with a controlled copper release (up to 84 ppm at a concentration of 1 mg/mL). This comprehensive understanding of the interplay between composition, textural properties, and bioactivity, offers insights for the design of tailored MBGNs for bone tissue regeneration with additional biological and antibacterial effects.

Based on interviews (N=146) conducted with academic actors from 2013 to 2017, this article investigates to what extend the academic affiliation shapes the conditions of possibility for partnerships between academics in the Humanities and Social Sciences (N=51) and non-academic actors, in a comparative perspective between Syracuse University (USA) and Paris Nanterre (France). The status of academic (tenured) is underlined as the main asset in terms of security and autonomy of work. On the other hand, some professional logics, driven by important transformation of the university organizations (especially in France) and academic norms, are presented as strong constraints, although modulated by disciplinary effects. Taking into account the growing role of the university of affiliation in the differentiation of working conditions and the access to professional resources (funding, partners, recognition), different strategies are implemented by the academics. These strategies are characterized by the adoption - with or without adhesion - of entrepreneurial logics, as a way of creating by oneself the favorable conditions to develop partnerships. Academics then seek to develop their own funds and become more dependent on private resources or competitive calls for projects, in order to finance their partnership projects, or even to use them to finance their other activities.

In the face of economic inequalities, redistribution of wealth is a key debate for society, and understanding the reasons why individuals may support more or less redistribution can inform this debate. Here we investigate the mechanisms by which experiencing success in a task decreases the support for redistribution of the wealth generated by the task, such that overachievers favor less redistribution than underachievers. In a laboratory experiment, we replicate this effect and explore how it that may be mediated by an in-group bias, or by changes in individuals’ principles of redistributive justice. Critically, both in-group favoritism and self-serving adjustments of justice principles partially accounted for the effect of status on redistribution choices. Our study thus sheds new light on the various ways by which economic experience affects support for redistribution.

The introduction of magnetism in two-dimensional (2D) materials represents an intense field of research nowadays and the quest to reach above-room-temperature ordering temperatures is still underway. Intrinsic ferromagnetism was discovered in 2017 in CrI$_{{3}}$ and Cr$_{{2}}$Ge$_{{2}}$Te$_{{6}}$ in the monolayer form with low Curie temperatures. An alternative method to introduce magnetism into conventional 2D materials is substitutional doping with magnetic impurities similarly to three-dimensional diluted magnetic semiconductors. The case of Mn-doped transition metal dichalcogenide (MoS$_{{2}}$, MoSe$_{{2}}$, WS$_{{2}}$, WSe$_{{2}}$) monolayers is very interesting because combining out-of-plane ferromagnetism and valley contrast leads to ferrovalley materials. In this work, we focus on the incorporation of Mn in MoSe$_{{2}}$ by molecular beam epitaxy on graphene which has been rarely addressed up to now. By using a multiscale characterization approach, we demonstrate that Mn atoms are incorporated into the MoSe$_{{2}}$ monolayer up to 5 atomic percent. However, when incorporated into the film, Mn atoms tend to diffuse to the grain edges forming undefined Mo$_{{{\it x}}}$Mn$_{{{\it y}}}$Se$_{{{\it z}}}$ phase at grain boundaries after completion of the MoSe$_{{2}}$ monolayer. This segregation leaves the crystalline and electronic structure of MoSe$_{{2}}$ unmodified. Above 5%, the saturation of Mn content in MoSe$_{{2}}$ leads to the formation of epitaxial MnSe clusters.

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10-12). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.

Sepsis is a life-threatening disease defined as an organ dysfunction caused by a dysregulated host response to an infection. Early diagnosis and prognosis of sepsis are necessary for specific and timely treatment. However, no predictive biomarkers or therapeutic targets are available yet, mainly due to the lack of a pertinent model. A better understanding of the pathophysiological mechanisms associated with sepsis will allow for earlier and more appropriate management. For this purpose, experimental models of sepsis have been set up to decipher the progression and pathophysiology of human sepsis but also to identify new biomarkers or therapeutic targets. These experimental models, although imperfect, have mostly been performed on a murine model. However, due to the different pathophysiology of the species, the results obtained in these studies are difficult to transpose to humans. This underlines the importance of identifying pertinent situations to improve patient care. As humans, horses have the predisposition to develop sepsis spontaneously and may be a promising model for spontaneous sepsis. This review proposes to give first an overview of the different animal species used to model human sepsis, and, secondly, to focus on adult equine sepsis as a spontaneous model of sepsis and its potential implications for human and veterinary medicine.

This review expands on a talk I gave during the 'Biology of Anthrax' meeting held in Bari, Italy (September 3rd–6th, 2019). The talk was a synthesis of recent investigations taking advantage of the topology of the Bacillus anthracis phylogenetic tree to propose tentative dating points and scenarios. Currently available whole-genome sequence (WGS) data allowed identifying single nucleotide polymorphisms (SNPs) among B. anthracis strains and drawing phylogenetic trees. The geographic origin of the strains and the topology of the tree were used to infer spreading events. Five star-like patterns in the tree (polytomies), each containing at least six branches, were detected. The analysis of the geographic distribution of the strains constituting one such polytomy suggests that it emerged not more than a few centuries ago. The key observation allowing this dating is the finding that the polytomy is anchored into Western Europe and that the main North-American lineage emerged from one of its branches, indicative of a post-Columbian export. From this point, I propose additional working hypotheses which may allow dating key nodes along the phylogeny of B. anthracis corresponding to four 'Out-of-Africa' events. While trade of contaminated animal products seems to be the predominant driving force underlying modern long-distance spreading of B. anthracis, invasive military operations and more generally borders instabilities may have played an important role in earlier times. The testing of these hypotheses will require the sequencing of a significant number of additional strains from many countries.

PurposeVarious food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults.MethodsThis study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders.ResultsMean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant.ConclusionsWe identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3' UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases.

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 × 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 × 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 × 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.

Neisseria meningitidis (meningococcus) is a cosmopolitan bacterium that is often found in the upper respiratory tract of asymptomatic humans. However, N. meningitidis also causes meningeal inflammation and/or sepsis in humans with a periodic resurgence in incidence and high mortality rates. The pathogen is highly diverse genetically and antigenically, so that genotyping is considered important for vaccine matching to circulating strains. Annual incidence of meningococcal disease in Kazakhstan ranges between 0.2 and 2.5 cases per 100 thousand population. In total, 78 strains of N. meningitidis were isolated from clinical patients and contact persons during the years 2017–2018 in Kazakhstan. Of these, 41 strains including four from the patients and 37 from contacts, were sequenced using Illumina MiSeq. In silico typing was completed using the Neisseria pipeline 1.2 on the Galaxy Workflow Management System and PubMLST. Whole genome SNP (single nucleotide polymorphisms) trees were built using BioNumerics 8. Seven-gene multilocus sequence typing (MLST) identified ten sequence types (ST), two of which have not been previously described (ST-16025; ST-16027). ST-16025 was detected in two patients with invasive meningococcal disease in 2017 and 2018 in Akmola region and 16 contacts in 2017 in Turkistan region. This prevalent type ST-16025 demonstrates considerable intertypic diversity as it consists of three subcomplexes with a distance of more than 2000 SNPs. Invasive and carrier strains belong to different serogroups (MenB and MenC), PorA and FetA_VR. Two invasive strains were MenB, one MenC and one MenW (Hajj lineage). The strains from the contact persons were: MenC (n = 18), cnl (n = 9), MenY (n = 7), MenW (n = 1), MenB (n = 1) and one unidentifiable. Different numbers of alleles were present: 12, 11, 7, and 7 alleles for PorA, FetA, fHbp, and NHBA, respectively. This study is the first report of the genetic diversity of N. meningitidis strains in Kazakhstan. Despite limitations with the studied sample size, important conclusions can be drawn based on data produced. This study provides evidence for regulatory authorities with regard to changing routine diagnostic protocols to increase the collecting of samples for WGS.

Atomically thin transition metal dichalcogenides possess a valley degree of freedom, which could enrich the physics underpinning the conventional Nernst effect observed in traditional solids. Here, the authors report experimental evidence of the valley Nernst effect in WSe2 at room temperature.

This article describes Bacillus anthracis strains isolated in Kazakhstan since the 1950s until year 2016 from sixty-one independent events associated with anthrax in humans and animals. One hundred and fifty-four strains were first genotyped by Multiple Locus VNTR (variable number of tandem repeats) Analysis (MLVA) using 31 VNTR loci. Thirty-five MLVA31 genotypes were resolved, 28 belong to the A1/TEA group, five to A3/Sterne-Ames group, one to A4/Vollum and one to the B clade. This is the first report of the presence of the B-clade in Kazakhstan. The MLVA31 results and epidemiological data were combined to select a subset of seventy-nine representative strains for draft whole genome sequencing (WGS). Strains from Kazakhstan significantly enrich the known phylogeny of the Ames group polytomy, including the description of a new branch closest to the Texas, United States A.Br.Ames sublineage stricto sensu. Three among the seven currently defined branches in the TEA polytomy are present in Kazakhstan, “Tsiankovskii”, “Heroin”, and “Sanitary Technical Institute (STI)”. In particular, strains from the STI lineage are largely predominant in Kazakhstan and introduce numerous deep branching STI sublineages, demonstrating a high geographic correspondence between “STI” and Kazakhstan, Central Asia. This observation is a strong indication that the TEA polytomy emerged after the last political unification of Asian steppes in the fourteenth century of the Common Era. The phylogenetic analysis of the Kazakhstan data and of currently available WGS data of worldwide origin strengthens our understanding of B. anthracis geographic expansions in the past seven centuries.

ABSTRACT Q (query) fever is an infectious zoonotic disease caused by the Gram-negative bacterium Coxiella burnetii. Although the disease has been studied for decades, it still represents a threat due to sporadic outbreaks across farms in Europe. The absence of a central platform for Coxiella typing data management is an important epidemiological gap that is relevant in the case of an outbreak. To fill this gap, we have designed and implemented an online, open-source, web-based platform called CoxBase (https://coxbase.q-gaps.de). This platform includes a database that holds genotyping information on more than 400 Coxiella isolates alongside metadata that annotate them. We have also implemented features for in silico genotyping of completely or minimally assembled Coxiella sequences using five different typing methods, querying of existing isolates, visualization of isolate geodata via aggregation on a world map, and submission of new isolates. We tested our in silico typing method on 50 Coxiella genomes downloaded from the RefSeq database, and we successfully genotyped all genomes except for cases where the sequence quality was poor. We identified new spacer sequences using our implementation of the multispacer sequence typing (MST) in silico typing method and established adaA gene phenotypes for all 50 genomes as well as their plasmid types. IMPORTANCE Q fever is a zoonotic disease that is a source of active epidemiological concern due to its persistent threat to public health. In this project, we have identified areas in the field of Coxiella research, especially regarding public health and genomic analysis, where there is an inadequacy of resources to monitor, organize, and analyze genomic data from C. burnetii. Subsequently, we have created an open, web-based platform that contains epidemiological information, genome typing functions comprising all the available Coxiella typing methods, and tools for isolate data discovery and visualization that could help address the above-mentioned challenges. This is the first platform to combine all disparate genotyping systems for Coxiella burnetii as well as metadata assets with tools for genomic comparison and analyses. This platform is a valuable resource for laboratory researchers as well as research epidemiologists interested in investigating the relatedness or dissimilarity among C. burnetii strains.

This article traces the contours and dynamics of the debates about the politics of gene editing. It does so by providing both a quantitative and qualitative analysis of the publications on the topic. We present a scientometric analysis of scientific publications; we discuss the geographies of gene editing by analysing the scales and spatial terms mobilised; and we undertake a lexicometric analysis of how debates are framed and the public is positioned. Our scientometric analysis of scientific articles shows that the governance and regulation of gene editing is discussed across an increasing range of disciplines and countries over the years. Along with this internationalisation and “transdisciplinarisation,” we see a qualitative shift in the “grounding” of the debate: while initially, authors tend to reflect about gene editing, in more recent years, there are increasing calls to act upon current knowledge. Across the countries we studied (the United States, the United Kingdom, Germany, China, Australia, Japan, and Canada) our lexicometric analysis shows only a few differences in terms of how gene editing is discussed. While the general framing of the debate is widely shared, the differences that we observe concern for instance the applications or benefits of gene editing and the ways in which the importance of involving the public is worded. We hold that bringing together multiple methods allows a rich and multifaceted discussion of the politics of gene editing, and that this opens up fertile dialogues between geography, sociology and political science.

The interconversion between spin and charge degrees of freedom offers incredible potential for spintronic devices, opening routes for spin injection, detection, and manipulation alternative to the use of ferromagnets. The understanding and control of such interconversion mechanisms, which rely on spin–orbit coupling, is therefore an exciting prospect. The emergence of van der Waals materials possessing large spin–orbit coupling (such as transition metal dichalcogenides or topological insulators) and/or recently discovered van der Waals layered ferromagnets further extends the possibility of spin-to-charge interconversion to ultrathin spintronic devices. Additionally, they offer abundant room for progress in discovering and analyzing novel spin–charge interconversion phenomena. Modifying the properties of van der Waals materials through proximity effects is an added degree of tunability also under exploration. This Perspective discusses the recent advances toward spin-to-charge interconversion in van der Waals materials. It highlights scientific developments which include techniques for large-scale growth, device physics, and theoretical aspects.