Properties and dynamics of meron topological spin textures in the two-dimensional magnet CrCl3

Merons are nontrivial topological spin textures highly relevant for many phenomena in solid state physics. Despite their importance, direct observation of such vortex quasiparticles is scarce and has been limited to a few complex materials. Here we show the emergence of merons and antimerons in recently discovered two-dimensional (2D) CrCl3 at zero magnetic field. We show their entire evolution from pair creation, their diffusion over metastable domain walls, and collision leading to large magnetic monodomains. Both quasiparticles are stabilized spontaneously during cooling at regions where in-plane magnetic frustration takes place. Their dynamics is determined by the interplay between the strong in-plane dipolar interactions and the weak out-of-plane magnetic anisotropy stabilising a vortex core within a radius of 8-10 nm. Our results push the boundary to what is currently known about non-trivial spin structures in 2D magnets and open exciting opportunities to control magnetic domains via topological quasiparticles.Comment: Nature Communications 12, 185 (2021). Editors' Highlights sectio

Mesenchymal Stem Cells for Treatment of CNS Injury

Brain and spinal cord injuries present significant therapeutic challenges. The treatments available for these conditions are largely ineffective, partly due to limitations in directly targeting the therapeutic agents to sites of pathology within the central nervous system (CNS). The use of stem cells to treat these conditions presents a novel therapeutic strategy. A variety of stem cell treatments have been examined in animal models of CNS trauma. Many of these studies have used stem cells as a cell-replacement strategy. These investigations have also highlighted the significant limitations of this approach. Another potential strategy for stem cell therapy utilises stem cells as a delivery mechanism for therapeutic molecules. This review surveys the literature relevant to the potential of mesenchymal stem cells for delivery of therapeutic agents in CNS trauma in humans

Ancient DNA Reveals Genetic Continuity in Mountain Woodland Caribou of the Mackenzie and Selwyn Mountains, Northwest Territories, Canada

We examine the mitochondrial genetic stability of mountain woodland caribou (Rangifer tarandus caribou) in the Mackenzie and Selwyn Mountains, Northwest Territories, over the last 4000 years. Unlike caribou populations in the Yukon, populations in the Northwest Territories show no evidence for mitochondrial genetic turnover during that period, which indicates that they were not adversely affected by the widespread deposition of the White River tephra around 1200 years ago. We detect moderate genetic differentiation between mountain woodland and barren-ground caribou in both territories, lending support to the current subspecies designations. In addition, we identify moderate genetic differentiation between Northwest Territories and western Yukon mountain woodland caribou, suggesting that there has been minimal mixing of matrilines between these herds.Nous examinons la stabilité génétique mitochondriale des caribous des bois des montagnes (Rangifer tarandus caribou) qui ont évolué dans les monts Mackenzie et dans la chaîne de Selwyn, Territoires du Nord-Ouest, ces 4 000 dernières années. Contrairement aux populations de caribou du Yukon, les populations de caribou des Territoires du Nord-Ouest ne montrent aucun signe de rotation génétique mitochondriale pendant cette période, ce qui indique qu’ils n’ont pas été affectés de manière défavorable par le dépôt à grande échelle du téphra de la rivière White, il y a environ 1 200 ans. Nous détectons une différentiation génétique modérée entre le caribou des bois des montagnes et le caribou de la toundra dans les deux territoires, ce qui vient appuyer les désignations actuelles de sous-espèces. Par ailleurs, nous avons dénoté une différenciation génétique modérée entre le caribou des bois des montagnes des Territoires du Nord-Ouest et celui de l’ouest du Yukon, ce qui laisse croire qu’il y aurait eu peu de mélanges matrilinéaires entre ces troupeaux

Probing the properties of convective cores through g modes: high-order g modes in SPB and gamma Doradus stars

In main sequence stars the periods of high-order gravity modes are sensitive probes of stellar cores and, in particular, of the chemical composition gradient that develops near the outer edge of the convective core. We present an analytical approximation of high-order g modes that takes into account the effect of the mu gradient near the core. We show that in main-sequence models, similarly to the case of white dwarfs, the periods of high-order gravity modes are accurately described by a uniform period spacing superposed to an oscillatory component. The periodicity and amplitude of such component are related, respectively, to the location and sharpness of the mu gradient. We investigate the properties of high-order gravity modes for stellar models in a mass domain between 1 and 10 Msun, and the effects of the stellar mass, evolutionary state, and extra-mixing processes on period spacing features. In particular, we show that for models of a typical SPB star, a chemical mixing that could likely be induced by the slow rotation observed in these stars, is able to significantly change the g-mode spectra of the equilibrium model. Prospects and challenges for the asteroseismology of gamma Doradus and SPB stars are also discussed.Comment: 18 pages, 29 figures, accepted for publication in MNRA

Testing the preservation potential of early diagenetic dolomites as geochemical archives

Early marine diagenetic dolomite is a rather thermodynamically‐stable carbonate phase and has potential to act as an archive of marine porewater properties. However, the variety of early to late diagenetic dolomite phases that can coexist within a single sample can result in extensive complexity. Here, the archive potential of early marine dolomites exposed to extreme post‐depositional processes is tested using various types of analyses, including: petrography, fluid inclusion data, stable δ13C and δ18O isotopes, 87Sr/86Sr ratios, and U‐Pb age dating of various dolomite phases. In this example, a Triassic carbonate platform was dissected and overprinted (diagenetic temperatures of 50 to 430°C) in a strike‐slip zone in Southern Spain. Eight episodes of dolomitization, a dolostone cataclasite and late stage meteoric/vadose cementation were recognized. The following processes were found to be diagenetically relevant: (i) protolith deposition and fabric‐preservation, and marine dolomitization of precursor aragonite and calcite during the Middle–Late Triassic; (ii) intermediate burial and formation of zebra saddle dolomite and precipitation of various dolomite cements in a Proto‐Atlantic opening stress regime (T ca 250°C) during the Early–Middle Jurassic; (iii) dolomite cement precipitation during early Alpine tectonism, rapid burial to ca 15 km, and high‐grade anchizone overprint during Alpine tectonic evolution in the Early Eocene to Early Miocene; (iv) brecciation of dolostones to cataclasite during the onset of the Carboneras Fault Zone activity during the Middle Miocene; and (v) late‐stage regression and subsequent meteoric overprint. Data shown here document that, under favourable conditions, early diagenetic marine dolomites and their archive data may resist petrographic and geochemical resetting over time intervals of 108 or more years. Evidence for this preservation includes preserved Late Triassic seawater δ13CDIC values and primary fluid inclusion data. Data also indicate that oversimplified statements based on bulk data from other petrographically‐complex dolomite archives must be considered with caution

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

IntroductionNon-muscle-invasive bladder cancer (NMIBC) is a common and heterogeneous disease; many patients develop recurrent or progress to muscle-invasive disease. Intravesical drug therapy is a pillar in the current management of NMIBC; notwithstanding, Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) have numerous limitations including international supply issues, and local and systemic toxicity. Here we review novel intravesical therapeutic options and drug delivery devices with potential for clinical use in the treatment of NMIBC.MethodsPubMed, ClinicalTrials.gov and Cochrane Library searches were undertaken. Systematic reviews, meta-analyses, randomised controlled trials, single-arm clinical trials and national/international conference proceedings were included.ResultsNovel intravesical drugs, including chemotherapeutic agents, immune checkpoint inhibitors, monoclonal antibodies and gene therapies, have demonstrated varying efficacy in the treatment of NMIBC. Current evidence for the majority of treatments is mostly limited to single-arm trials in patients with recurrent NMIBC. Various novel methods of drug delivery have also been investigated, with encouraging preliminary results supporting the intravesical delivery of hyperthermic MMC and MMC hydrogel formulations.ConclusionsNovel therapeutic agents and drug delivery systems will be important in the future intravesical management of NMIBC. As our understanding of the molecular diversity of NMIBC develops, molecular subtyping will become fundamental in the personalisation of intravesical treatments. Further randomised studies are urgently required to investigate the efficacy of novel intravesical treatments and novel regimens, in comparison to current standards-of-care, particularly in the context of international BCG shortages

Developmental switch of intestinal antimicrobial peptide expression

Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period

Web-based alcohol intervention:study of systematic attrition of heavy drinkers

Background: Web-based alcohol interventions are a promising way to reduce alcohol consumption because of their anonymity and the possibility of reaching a high numbers of individuals including heavy drinkers. However, Web-based interventions are often characterized by high rates of attrition. To date, very few studies have investigated whether individuals with higher alcohol consumption show higher attrition rates in Web-based alcohol interventions as compared with individuals with lower alcohol consumption. Objectives: The aim of this study was to examine the attrition rate and predictors of attrition in a Web-based intervention study on alcohol consumption. Methods: The analysis of the predictors of attrition rate was performed on data collected in a Web-based randomized control trial. Data collection took place at the University of Konstanz, Germany. A total of 898 people, which consisted of 46.8% males (420/898) and 53.2% females (478/898) with a mean age of 23.57 years (SD 5.19), initially volunteered to participate in a Web-based intervention study to reduce alcohol consumption. Out of the sample, 86.9% (781/898) were students. Participants were classified as non-completers (439/898, 48.9%) if they did not complete the Web-based intervention. Potential predictors of attrition were self-reported: alcohol consumption in the last seven days, per week, from Monday to Thursday, on weekends, excessive drinking behavior measured with the Alcohol Use Disorder Identification Test (AUDIT), and drinking motives measured by the Drinking Motive Questionnaire (DMQ-R SF). Results: Significant differences between completers and non-completers emerged regarding alcohol consumption in the last seven days (B=-.02, P=.05, 95% CI [0.97-1.00]), on weekends (B=-.05, P=.003, 95% CI [0.92-0.98]), the AUDIT (B=-.06, P=.007, 95% CI [0.90-0.98], and the status as a student (B=.72, P=.001, 95% CI [1.35-3.11]). Most importantly, non-completers had a significantly higher alcohol consumption compared with completers. Conclusions: Hazardous alcohol consumption appears to be a key factor of the dropout rate in a Web-based alcohol intervention study. Thus, it is important to develop strategies to keep participants who are at high risk in Web-based interventions

Fungal microbiota dysbiosis in IBD.

International audienceThe bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis

Cumulative Inflammatory Load Is Associated with Short Leukocyte Telomere Length in the Health, Aging and Body Composition Study

Background: Leukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction. Methodology/Principal Findings: To address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70-79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-α had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-α had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37-0.72), only IL-6 high (OR = 0.57, CI = 0.39-0.83) or only TNF-α high (OR = 0.67, CI = 0.46-0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL. Conclusions/Significance: Results suggest that cumulative inflammatory load, as indexed by the combination of high levels of IL-6 and TNF-α, is associated with increased odds for short LTL. In contrast, high levels of CRP were not accompanied by short LTL in this cohort of older adults. These data provide the first large-scale demonstration of links between inflammatory markers and LTL in an older population