5S-IGS rDNA in wind-pollinated trees (Fagus L.) encapsulates 55 million years of reticulate evolution and hybrid origins of modern species

Standard models of plant speciation assume strictly dichotomous genealogies in which a species, the ancestor, is replaced by two offspring species. The reality in wind‐pollinated trees with long evolutionary histories is more complex: species evolve from other species through isolation when genetic drift exceeds gene flow; lineage mixing can give rise to new species (hybrid taxa such as nothospecies and allopolyploids). The multi‐copy, potentially multi‐locus 5S rDNA is one of few gene regions conserving signal from dichotomous and reticulate evolutionary processes down to the level of intra‐genomic recombination. Therefore, it can provide unique insights into the dynamic speciation processes of lineages that diversified tens of millions of years ago. Here, we provide the first high‐throughput sequencing (HTS) of the 5S intergenic spacers (5S‐IGS) for a lineage of wind‐pollinated subtropical to temperate trees, the Fagus crenata – F. sylvatica s.l. lineage, and its distant relative F. japonica. The observed 4963 unique 5S‐IGS variants reflect a complex history of hybrid origins, lineage sorting, mixing via secondary gene flow, and intra‐genomic competition between two or more paralogous‐homoeologous 5S rDNA lineages. We show that modern species are genetic mosaics and represent a striking case of ongoing reticulate evolution during the past 55 million years

Discrete element simulation and experimental study of powder spreading process in additive manufacturing

Powders used in additive manufacturing (AM) are spread into a compact layer of particles for sintering and this process is repeated layer by layer to form the final products. Spreading of rod-shaped particles in realistic AM settings is simulated using the discrete element method (DEM) to investigate the effects of particle shape and operating conditions on the bed quality, characterised by its surface roughness and solid volume fraction. It is discovered that larger particle aspect ratios, Ar, or higher spreader translational velocities result in a lower bed quality, i.e. a larger surface roughness and a smaller volume fraction. The surface roughness increases monotonically with Ar. However, the volume fraction exhibits a maximum at Ar = 1.5 for randomly packed powder beds that are formed by the roller type spreaders moving at low translational velocities. It is also found that a roller outperforms a blade spreader in terms of the quality of the prepared bed at the same operating conditions. The micro-structural analysis of the beds also shows particle alignment in response to the induced flow, which is qualitatively confirmed by a set of purposely-designed experiments. In addition, a shape segregation is documented for powders with mixed aspect ratios (Ar) such that particles with larger Ar tend to accumulate on the upper layers of the bed

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

sharma et al. define a new primary atopic disorder caused by heterozygous gain-of-function variants in STAT6. this results in severe, early-onset allergies, and is seen in 16 patients from 10 families. Anti-IL-4R & alpha; antibody and JAK inhibitor treatment were highly effective.STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. we have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. the cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). all patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and T(H)2 skewing. Precision treatment with the anti-IL-4R & alpha; antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. this study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

Selective laser sintering of calcium polyphosphate - Polyvinyl alcohol for biomedical applications

It is widely recognized that layered manufacturing techniques have the potential to make an important contribution in medicine. One of the most exciting areas of their application is the production of the bone-interfacing implants currently used in orthopaedics and dentistry. This article studies the laser sintering of a mixture of Calcium Polyphosphate (CPP) and Polyvinyl Alcohol (PVA) to make structures with possible applications in such areas. An experimental study of the creation of the green part is performed to identify the effects of different process parameters such as laser power and scanning speed. The work indicated that the CPP-PVA sintered layer thickness can be adjusted by controlling the laser sintering process parameters. The fabricated samples can be either utilized as composite bio-structures or considered as green parts for post-densification through conventional sintering