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Purpose Reconstruction of the Anterior cruciate ligament (ACL) using tendon grafting is an established method for restoring knee function and stability. Multiple methods are established for graft fixation. Several involve anchoring the autograft distant to the joint with hardware that remains implanted. This study reports the first early to midterm results in patients who received ACL reconstruction (ACLR) using the T-Lock Osteotrans femoral near joint fixation method with a tibial fixation using the BioactIF Osteotrans interference screw. Methods This consecutive prospective series included 20 Patients (14 Male, 6 Female) with a primary ACL rupture. All patients were treated with an ACLR using a semitendinosus autograft fixated with the T-Lock Osteotrans and were followed-up postoperatively. The following parameters were assessed: Side-to-side difference of the posterior-anterior translation measured using the KT-1000 arthrometer, Tegner activity score, Lysholm score, IKDC subjective knee evaluation form. Magnetic resonance imaging (MRI) was done to assess tunnel enlargement and integrity of the anchoring device. Results The average follow-up duration was 2 years (range 1–4.2 years). One patient was lost to follow-up. Two Patients suffered a traumatic ACL re-rupture 2 years postoperatively and received a 2-stage revision ACLR. Difference in the posterior-anterior translation was 1.8 mm (range 0–5). The median Tegner score was 6 (range 4–10) and 9 patients (45%) returned to their preinjury level of activity. The mean IKDC subjective knee evaluation form scored 91 points (range 77–100). The mean Lysholm score was 86 points (74–96). All mentioned scores were significantly better compared to preoperative values. No relevant tunnel enlargement was seen on MRI. The anchoring device was evaluated to be intact in all patients. Conclusion ACLR with the aforementioned procedure leads to good clinical and radiological outcome.

Bicuspid aortic valve (BAV) is a common congenital heart defect (population incidence, 1–2%) 1 – 3 that frequently presents with ascending aortic aneurysm (AscAA) 4 . BAV/AscAA shows autosomal dominant inheritance with incomplete penetrance and male predominance. Causative gene mutations (for example, NOTCH1 , SMAD6 ) are known for ≤1% of nonsyndromic BAV cases with and without AscAA 5 – 8 , impeding mechanistic insight and development of therapeutic strategies. Here, we report the identification of variants in ROBO4 (which encodes a factor known to contribute to endothelial performance) that segregate with disease in two families. Targeted sequencing of ROBO4 showed enrichment for rare variants in BAV/AscAA probands compared with controls. Targeted silencing of ROBO4 or mutant ROBO4 expression in endothelial cell lines results in impaired barrier function and a synthetic repertoire suggestive of endothelial-to-mesenchymal transition. This is consistent with BAV/AscAA-associated findings in patients and in animal models deficient for ROBO4. These data identify a novel endothelial etiology for this common human disease phenotype. Individuals with biscuspid aortic valve and ascending aortic aneurysm show enrichment of rare variants in ROBO4 . Functional studies suggest that ROBO4 mutations disrupt endothelial cell performance and contribute to pathological remodeling of aortic tissues.

Bicuspid aortic valve (BAV) is the most common congenital heart defect (CHD), affecting 1–2% of the population. BAV is associated with thoracic aortic aneurysms (TAAs). Deleterious copy number variations (CNVs) were found previously in up to 10% of CHD cases. This study aimed at unravelling the contribution of deleterious deletions or duplications in 95 unrelated BAV/TAA patients. Seven unique or rare CNVs were validated, harbouring protein-coding genes with a role in the cardiovascular system. Based on the presence of overlapping CNVs in patients with cardiovascular phenotypes in the DECIPHER database, the identification of similar CNVs in whole-exome sequencing data of 67 BAV/TAA patients and suggested topological domain involvement from Hi-C data, supportive evidence was obtained for two genes (DGCR6 and TBX20) of the seven initially validated CNVs. A rare variant burden analysis using next-generation sequencing data from 637 BAV/TAA patients was performed for these two candidate genes. This revealed a suggestive genetic role for TBX20 in BAV/TAA aetiology, further reinforced by segregation of a rare TBX20 variant with the phenotype within a BAV/TAA family. To conclude, our results do not confirm a significant contribution for deleterious CNVs in BAV/TAA as only one potentially pathogenic CNV (1.05%) was identified. We cannot exclude the possibility that BAV/TAA is occasionally attributed to causal CNVs though, or that certain CNVs act as genetic risk factors by creating a sensitised background for BAV/TAA. Finally, accumulative evidence for TBX20 involvement in BAV/TAA aetiology underlines the importance of this transcription factor in cardiovascular disease.

Abstract Retrophylogenomics makes use of genome-wide retrotransposon presence/absence insertion patterns to resolve questions in phylogeny and population genetics. In the genomics era, evaluating high-throughput data requires the associated development of appropriately powerful statistical tools. The currently used KKSC 3-lineage statistical test for evaluating the significance of data is limited by the number of possible tree topologies it can assess in one step. To improve on this, we have now extended the analysis to simultaneously compare 4-lineages, which now enables us to evaluate ten distinct presence/absence insertion patterns for 26 possible tree topologies plus 129 trees with different incidences of hybridization. Moreover, the new tool includes statistics for multiple ancestral hybridizations, ancestral incomplete lineage sorting, bifurcation, and polytomy. The test is embedded in a user-friendly web R-application (http://retrogenomics.uni-muenster.de:3838/hammlet/) and is available for use by the general scientific community. Competing Interest Statement The authors have declared no competing interest.

Congenital Heart Disease (CHD) affects approximately 7-9 children per 1000 live births. Numerous genetic studies have established a role for rare genomic variants at the copy number variation (CNV) and single nucleotide variant level. In particular, the role of de novo mutations (DNM) has been highlighted in syndromic and non-syndromic CHD. To identify novel haploinsufficient CHD disease genes we performed an integrative analysis of CNVs and DNMs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm (TAA). We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed mutation rate testing for DNMs identified in 2,489 parent-offspring trios. Our combined analysis revealed 21 genes which were significantly affected by rare genomic deletions and/or constrained non-synonymous de novo mutations in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in singletons and small cases series, or show new associations with CHD. In addition, a systems level analysis revealed shared contribution of CNV deletions and DNMs in CHD probands, affecting protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes.

Pollen records from large lakes have been used for quantitative palaeoclimate reconstruction, but the influences that lake size (as a result of species-specific variations in pollen dispersal patterns that smaller pollen grains are more easily transported to lake centre) and taphonomy have on these climatic signals have not previously been systematically investigated. We introduce the concept of pollen source area to pollen-based climate calibration using the north-eastern Tibetan Plateau as our study area. We present a pollen data set collected from large lakes in the arid to semi-arid region of central Asia. The influences that lake size and the inferred pollen source areas have on pollen compositions have been investigated through comparisons with pollen assemblages in neighbouring lakes of various sizes. Modern pollen samples collected from different parts of Lake Donggi Cona (in the north-eastern part of the Tibetan Plateau) reveal variations in pollen assemblages within this large lake, which are interpreted in terms of the species-specific dispersal and depositional patterns for different types of pollen, and in terms of fluvial input components. We have estimated the pollen source area for each lake individually and used this information to infer modern climate data with which to then develop a modern calibration data set, using both the multivariate regression tree (MRT) and weighted-averaging partial least squares (WA-PLS) approaches. Fossil pollen data from Lake Donggi Cona have been used to reconstruct the climate history of the north-eastern part of the Tibetan Plateau since the Last Glacial Maximum (LGM). The mean annual precipitation was quantitatively reconstructed using WA-PLS: extremely dry conditions are found to have dominated the LGM, with annual precipitation of around 100 mm, which is only 32% of present-day precipitation. A gradually increasing trend in moisture conditions during the Late Glacial is terminated by an abrupt reversion to a dry phase that lasts for about 1000 yr and coincides with \"Heinrich event 1\" in the North Atlantic region. Subsequent periods corresponding to the Bølling/Allerød interstadial, with annual precipitation (Pann) of about 350 mm, and the Younger Dryas event (about 270 mm Pann) are followed by moist conditions in the early Holocene, with annual precipitation of up to 400 mm. A drier trend after 9 cal. ka BP is followed by a second wet phase in the middle Holocene, lasting until 4.5 cal. ka BP. Relatively steady conditions with only slight fluctuations then dominate the late Holocene, resulting in the present climatic conditions. The climate changes since the LGM have been primarily driven by deglaciation and fluctuations in the intensity of the Asian summer monsoon that resulted from changes in the Northern Hemisphere summer solar insolation, as well as from changes in the North Atlantic climate through variations in the circulation patterns and intensity of the westerlies.

The Moon experienced an intense period of impacts about 4 Gyr ago. This cataclysm is thought to have affected the entire inner Solar System and has been constrained by the radiometric dating of lunar samples: 40 Ar– 39 Ar ages reflect the heating and degassing of target rocks by large basin-forming impacts on the Moon. Radiometric dating of meteorites from Vesta and the H-chondrite parent body also shows numerous 40 Ar– 39 Ar ages between 3.4 and 4.1 Gyr ago, despite a different dynamical context, where impacts typically occur at velocities too low to reset geochronometers. Here we interpret the 40 Ar– 39 Ar age record in meteorites to reflect unusually high impact velocities exceeding 10 km s −1 . Compared with typical impact velocities for main-belt asteroids of about 5 km s −1 , these collisions would produce 100–1,000 times more highly heated material by volume. We propose that the 40 Ar– 39 Ar ages between 3.4 and 4.1 Gyr ago from Vesta, the H-chondrite parent body and the Moon record impacts from numerous main-belt asteroids that were driven onto high-velocity and highly eccentric orbits by the effects of the late migration of the giant planets. We suggest that the bombardment persisted for many hundreds of millions of years and affected most inner Solar System bodies. Lunar samples suggest that the inner Solar System was bombarded by asteroids about 4 Gyr ago. Radiometric ages of meteorites suggest an unusual number of high-velocity asteroids at this time, consistent with a dynamical origin of the bombardment in which the asteroids were pushed by outer planet migration onto highly eccentric orbits.

On 26 September 2022, NASA’s Double Asteroid Redirection Test (DART) mission successfully impacted Dimorphos, the natural satellite of the binary near-Earth asteroid (65803) Didymos. Numerical simulations of the impact provide a means to find the surface material properties and structures of the target that are consistent with the observed momentum deflection efficiency, ejecta cone geometry and ejected mass. Our simulation that best matches the observations indicates that Dimorphos is weak, with a cohesive strength of less than a few pascals, like asteroids (162173) Ryugu and (101955) Bennu. We find that the bulk density of Dimorphos ρ B is lower than ~2,400 kg m − 3 and that it has a low volume fraction of boulders (≲40 vol%) on the surface and in the shallow subsurface, which are consistent with data measured by the DART experiment. These findings suggest that Dimorphos is a rubble pile that might have formed through rotational mass shedding and reaccumulation from Didymos. Our simulations indicate that the DART impact caused global deformation and resurfacing of Dimorphos. ESA’s upcoming Hera mission may find a reshaped asteroid rather than a well-defined crater. Numerical simulations of the DART impact on asteroid Didymos’s moon Dimorphos highlight its rubble-pile nature with a low bulk density and boulder volume fraction. These results indicate that Dimorphos formed from reaccumulated material shed from Didymos via rotation or impact.

This paper reviews habitability conditions for a terrestrial planet from the point of view of geosciences. It addresses how interactions between the interior of a planet or a moon and its atmosphere and surface (including hydrosphere and biosphere) can affect habitability of the celestial body. It does not consider in detail the role of the central star but focusses more on surface conditions capable of sustaining life. We deal with fundamental issues of planetary habitability, i.e. the environmental conditions capable of sustaining life, and the above-mentioned interactions can affect the habitability of the celestial body. We address some hotly debated questions including: How do core and mantle affect the evolution and habitability of planets? What are the consequences of mantle overturn on the evolution of the interior and atmosphere? What is the role of the global carbon and water cycles? What influence do comet and asteroid impacts exert on the evolution of the planet? How does life interact with the evolution of the Earth’s geosphere and atmosphere? How can knowledge of the solar system geophysics and habitability be applied to exoplanets? In addition, we address the identification of preserved life tracers in the context of the interaction of life with planetary evolution.

Extra-tropical circulation systems impede poleward moisture advection by the Indian Summer Monsoon. In this context, the Himalayan range is believed to insulate the south Asian circulation from extra-tropical influences and to delineate the northern extent of the Indian Summer Monsoon in central Asia. Paleoclimatic evidence, however, suggests increased moisture availability in the Early Holocene north of the Himalayan range which is attributed to an intensification of the Indian Summer Monsoon. Nevertheless, mechanisms leading to a surpassing of the Himalayan range and the northern maximum extent of summer monsoonal influence remain unknown. Here we show that the Kunlun barrier on the northern Tibetan Plateau [~36°N] delimits Indian Summer Monsoon precipitation during the Holocene. The presence of the barrier relocates the insulation effect 1,000 km further north, allowing a continental low intensity branch of the Indian Summer Monsoon which is persistent throughout the Holocene. Precipitation intensities at its northern extent seem to be driven by differentiated solar heating of the Northern Hemisphere indicating dependency on energy-gradients rather than absolute radiation intensities. The identified spatial constraints of monsoonal precipitation will facilitate the prediction of future monsoonal precipitation patterns in Central Asia under varying climatic conditions.