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Chondrocyte differentiation controls skeleton development and stature. Here we provide a comprehensive map of chondrocyte-specific enhancers and show that they provide a mechanistic framework through which non-coding genetic variants can influence skeletal development and human stature. Working with fetal chondrocytes isolated from mice bearing a Col2a1 fluorescent regulatory sensor, we identify 780 genes and 2'704 putative enhancers specifically active in chondrocytes using a combination of RNA-seq, ATAC-seq and H3K27ac ChIP-seq. Most of these enhancers (74%) show pan-chondrogenic activity, with smaller populations being restricted to limb (18%) or trunk (8%) chondrocytes only. Notably, genetic variations overlapping these enhancers better explain height differences than those overlapping non-chondrogenic enhancers. Finally, targeted deletions of identified enhancers at the Fgfr3, Col2a1, Hhip and, Nkx3-2 loci confirm their role in regulating cognate genes. This enhancer map provides a framework for understanding how genes and non-coding variations influence bone development and diseases.

Abstract Spending time in forests benefits human well‐being, but the importance of forest characteristics on well‐being is unclear. This knowledge could help guide forest management decisions to improve outcomes for both people and nature. The overall aim of this study was to investigate how psychological restoration, defined as psychological recovery processes in nature, may be supported by forest characteristics. We (1) investigated how perceptions of restoration (perceived restorativeness) were linked to specific forest characteristics. More specifically, we selected attributes included in nature protection legislation in Germany (beauty, diversity and uniqueness) as the basis to evaluate how forest characteristics were related to perceived restorativeness. Additionally, we (2) tested differences in the assessments of these attributes between forestry experts and people from the general public. Based on the results of the first two objectives (1, 2), we (3) predicted how forest management that affects forest characteristics may impact psychological restoration today and in the future. We developed a perceived restorativeness model based on attributes stated in the German Nature Conservation Act and specific forest structure variables. Drawing from the literature, we included perceived naturalness as an additional key predictor for restoration. Forestry experts and participants from the general public were then asked to rate computer‐generated forest stand pictures on these attributes and restorativeness. We found that all attributes were positively associated with perceived restorativeness, but perceived beauty was most important. Perceived uniqueness was statistically significant, but the strength of the relationship was weak. Mixed forests were rated as most beautiful, while coniferous forest stands were rated as least beautiful. The general public gave higher ratings than forestry experts on all attributes, but the pattern was similar. Based on participant ratings, forests left without management (Set‐aside), followed by forests with management aiming for resilience to climate change (Adaptation forestry), both supporting biodiversity conservation, showed the highest perceived restorativeness over the course of 100 years. Based on our results, it could be recommendable to increase forest diversity, especially in areas with many visitors. However, more nuanced knowledge involving diverse stakeholders is needed to inform forest management decisions on landscape level. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Chondrocyte differentiation controls skeleton development and stature. Here we provide a comprehensive map of chondrocyte-specific enhancers and show that they provide a mechanistic framework through which non-coding genetic variants can influence skeletal development and human stature. Working with fetal chondrocytes isolated from mice bearing a Col2a1 fluorescent regulatory sensor, we identify 780 genes and 2'704 putative enhancers specifically active in chondrocytes using a combination of RNA-seq, ATAC-seq and H3K27ac ChIP-seq. Most of these enhancers (74%) show pan-chondrogenic activity, with smaller populations being restricted to limb (18%) or trunk (8%) chondrocytes only. Notably, genetic variations overlapping these enhancers better explain height differences than those overlapping non-chondrogenic enhancers. Finally, targeted deletions of identified enhancers at the Fgfr3, Col2a1, Hhip and, Nkx3-2 loci confirm their role in regulating cognate genes. This enhancer map provides a framework for understanding how genes and non-coding variations influence bone development and diseases.

After the end of World War I, Eastern Europe entered a period of upheaval. The continental empires dissolved and new nation-states emerged. Following the ideas of Woodrow Wilson, democratization became the dominant political concept. But the meaning of “democracy” was unclear, and many different political groups claimed sovereignty over its interpretation. In this article, we want to take a closer look at the border regions between the newly emerg-ing nation-states of Germany, Czechoslovakia, and Poland, which were characterized by a high degree of ethnic, religious, and social diversity. These border regions were also charac-terized by different experiences with politics, especially with voting rights and political parties. Despite their relative geographic proximity, Upper Silesia, Teschen Silesia, and Orava had very different political histories, being part of Prussia, the Austrian Crown Lands, andthe Kingdom of Hungary. While voting rights in the Kingdom of Hungary were severely restricted, the Austrian Crown Lands had universal male suffrage since 1907. In many cases, the concept of national belonging was very different from the political centersand often had a strong regional connotation—with regionalist movements claiming the idea of “self-deter-mination” for themselves. Thus, the regional conceptions of democracy and nationality that emerged in the brief period of 1918/19 are often unique and overlooked.

Abstract Subaqueous paleoseismic studies used soft sediment deformation structures (SSDS) to discern the shaking strength of past earthquakes, as the deformation degree of SSDS related to Kelvin Helmholtz Instability evolves from disturbed lamination and folds to intraclast breccia with higher peak ground accelerations (PGA). We lack comparative studies of different sediment types with SSDS related to earthquakes from different seismogenic sources to comprehend how these factors modulate earthquake‐induced deformation. Here, we compile sediment records with seven earthquake‐triggered SSDS from 10 lakes with organic‐, carbonate‐, siliciclastic‐, and diatom‐rich sediment from three subduction zones and one collisional setting. We target basin sequences with slope angles 0.65°. Fine‐grained clastics enhance sediment susceptibility to deformation, whereas abundant diatoms reduce it, demonstrating the influence of composition. Deformation correlates best with PGA and the vicinity of the earthquakes, suggesting that high frequency shaking promotes deformation. In addition, deformation only occurs above a minimum magnitude dependent on sediment composition, and higher deformation degrees in our studied basin sedimentary sequences only above Mw 4.9 for all sediment types, suggesting that sufficient duration of shaking—magnitude correlates with duration—is essential for SSDS development. We advise taking multiple cores on gentle slopes to study SSDS—additional to basin cores—to resolve small magnitude local earthquakes and relative differences in frequency content of past events.

The Varved Sediments Database (VARDA) was launched in 2020 and aimed to establish a community database for annually resolved chronological archives with their associated high-resolution proxy records. This resource would support reproducibility through accessible data for the paleoclimate and modelling communities. In this paper, VARDA has been extended by a dataset of European tephra geochemical data and metadata to enable the synchronisation of varve records during the Last Glacial–Interglacial Transition (LGIT; here defined as 25 to 8 ka; Beckett et al., 2022). Geochemical data from 49 known individual tephra layers across 19 lake records have been included, with Lago di Grande Monticchio being the single biggest contributor of geochemical data with 28 tephra layers. The Vedde Ash and Laacher See tephra are the most common layers found in six different records. This highlights the potential of refining the absolute age estimates for these tephra layers using varve chronologies and for synchronising regional paleoclimate archives. This is the first stage in a 5-year plan funded by the Past Global Changes (PAGES) Data Stewardship Scholarship to incorporate a global dataset of tephra geochemical data into varve records. Further stages of this project will focus on different regions and timescales. Data collated for this project are available open access at https://doi.org/10.5880/fidgeo.2023.015 (Beckett et al., 2022).

In slowly deforming tectonic settings (e.g., European Alps), large earthquakes occur too infrequently to be adequately represented in instrumental and historical records. This leads to uncertainties and inaccuracies of seismic hazard estimations. To extend the seismic record, lacustrine paleoseismologists usually resort to the sedimentary archive of large lakes where earthquakes can be recorded as mass-transport deposits and associated turbidites. The imprint of seismic shaking is generally more subtle and poorly understood in small lakes (

The understanding of the mechanisms for the development of ascites has evolved over the years, involving the liver, peritoneum, heart, and kidneys as key responsible for its formation. In this article, we review the pathophysiology of ascites formation, introducing the role of the intestine as a major responsible for ascites production through “a game changer” case.

An analysis of cis-regulatory domains (CRDs) among monocytes, neutrophils, and T cells derived from ChIP-seq peaks and methylation data suggests cell-type specific regulatory mechanisms of immunity.

ABSTRACT One of the most popular semantic representation languages in Natural Language Processing (NLP) is Abstract Meaning Representation (AMR). This formalism encodes the meaning of single sentences in directed rooted graphs. For English, there is a large annotated corpus that provides qualitative and reusable data for building or improving existing NLP methods and applications. For building AMR corpora for non-English languages, including Brazilian Portuguese, automatic and manual strategies have been conducted. The automatic annotation methods are essentially based on the cross-linguistic alignment of parallel corpora and the inheritance of the AMR annotation. The manual strategies focus on adapting the AMR English guidelines to a target language. Both annotation strategies have to deal with some phenomena that are challenging. This paper explores in detail some characteristics of Portuguese for which the AMR model had to be adapted and introduces two annotated corpora: AMRNews, a corpus of 870 annotated sentences from journalistic texts, and OpiSums-PT-AMR, comprising 404 opinionated sentences in AMR.

Experiments on ASDEX Upgrade (AUG) in 2021 and 2022 have addressed a number of critical issues for ITER and EU DEMO. A major objective of the AUG programme is to shed light on the underlying physics of confinement, stability, and plasma exhaust in order to allow reliable extrapolation of results obtained on present day machines to these reactor-grade devices. Concerning pedestal physics, the mitigation of edge localised modes (ELMs) using resonant magnetic perturbations (RMPs) was found to be consistent with a reduction of the linear peeling-ballooning stability threshold due to the helical deformation of the plasma. Conversely, ELM suppression by RMPs is ascribed to an increased pedestal transport that keeps the plasma away from this boundary. Candidates for this increased transport are locally enhanced turbulence and a locked magnetic island in the pedestal. The enhanced D-alpha (EDA) and quasi-continuous exhaust (QCE) regimes have been established as promising ELM-free scenarios. Here, the pressure gradient at the foot of the H-mode pedestal is reduced by a quasi-coherent mode, consistent with violation of the high-n ballooning mode stability limit there. This is suggestive that the EDA and QCE regimes have a common underlying physics origin. In the area of transport physics, full radius models for both L- and H-modes have been developed. These models predict energy confinement in AUG better than the commonly used global scaling laws, representing a large step towards the goal of predictive capability. A new momentum transport analysis framework has been developed that provides access to the intrinsic torque in the plasma core. In the field of exhaust, the X-Point Radiator (XPR), a cold and dense plasma region on closed flux surfaces close to the X-point, was described by an analytical model that provides an understanding of its formation as well as its stability, i.e., the conditions under which it transitions into a deleterious MARFE with the potential to result in a disruptive termination. With the XPR close to the divertor target, a new detached divertor concept, the compact radiative divertor, was developed. Here, the exhaust power is radiated before reaching the target, allowing close proximity of the X-point to the target. No limitations by the shallow field line angle due to the large flux expansion were observed, and sufficient compression of neutral density was demonstrated. With respect to the pumping of non-recycling impurities, the divertor enrichment was found to mainly depend on the ionisation energy of the impurity under consideration. In the area of MHD physics, analysis of the hot plasma core motion in sawtooth crashes showed good agreement with nonlinear 2-fluid simulations. This indicates that the fast reconnection observed in these events is adequately described including the pressure gradient and the electron inertia in the parallel Ohm’s law. Concerning disruption physics, a shattered pellet injection system was installed in collaboration with the ITER International Organisation. Thanks to the ability to vary the shard size distribution independently of the injection velocity, as well as its impurity admixture, it was possible to tailor the current quench rate, which is an important requirement for future large devices such as ITER. Progress was also made modelling the force reduction of VDEs induced by massive gas injection on AUG. The H-mode density limit was characterised in terms of safe operational space with a newly developed active feedback control method that allowed the stability boundary to be probed several times within a single discharge without inducing a disruptive termination. Regarding integrated operation scenarios, the role of density peaking in the confinement of the ITER baseline scenario (high plasma current) was clarified. The usual energy confinement scaling ITER98( p,y ) does not capture this effect, but the more recent H20 scaling does, highlighting again the importance of developing adequate physics based models. Advanced tokamak scenarios, aiming at large non-inductive current fraction due to non-standard profiles of the safety factor in combination with high normalised plasma pressure were studied with a focus on their access conditions. A method to guide the approach of the targeted safety factor profiles was developed, and the conditions for achieving good confinement were clarified. Based on this, two types of advanced scenarios (‘hybrid’ and ‘elevated’ q -profile) were established on AUG and characterised concerning their plasma performance.

This article provides a systematic review of the literature pertaining to students with Autism Spectrum Disorder (ASD) and the potential role of family members in higher education settings. The research questions guiding the review included: (a) What is the identified role(s) of family members of postsecondary students with ASD in postsecondary educational settings? and (b) Does family involvement in postsecondary education settings result in positive outcomes for students with ASD? The search terms, "Autism Spectrum Disorder," "familial involvement," "postsecondary education," and "educational success" and appropriate synonyms, yielded six articles that fit the inclusion criteria for this review: empirically-based studies conducted in the United States, either dissertations or peer-reviewed articles, published between the years 2003 and 2014, and included some mention of family support or involvement for college students with ASD. Given the very small sample of articles that met the criteria for this review and the limitations of each article, not enough research on family involvement exists to answer the research questions. It is unclear whether or not family members should be involved in postsecondary educational settings, what their potential roles might be, and if family member involvement would be beneficial for students with ASD.