Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans

Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.

Ratios of T-cell immune-effectors with tumour associated macrophages and PD-1/PD-L1 axis immune-checkpoint molecules, as prognosticators in diffuse large B cell lymphoma: A population-based study

Background Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured despite initial R-CHOP. Although the prognostic importance of the tumour microenvironment (TME) is established, the optimal strategy to quantify it is unknown. Methods The relationship between immune-effector and inhibitory (checkpoint) genes was assessed by NanoString™ in 252 paraffin-embedded DLBCL tissues. A model to quantify net anti-tumoural immunity as an outcome predictor was tested in 158 R-CHOP treated patients, and validated in tissue/blood from two independent R-CHOP treated cohorts of 233 and 140 patients respectively. Findings T and NK-cell immune-effector molecule expression correlated with tumour associated macrophage and PD-1/PD-L1 axis markers consistent with malignant B-cells triggering a dynamic checkpoint response to adapt to and evade immune-surveillance. A tree-based survival model was performed to test if immune-effector to checkpoint ratios were prognostic. The CD4*CD8:(CD163/CD68)*PD-L1 ratio was better able to stratify overall survival than any single or combination of immune markers, distinguishing groups with disparate 4-year survivals (92% versus 47%). The immune ratio was independent of and added to the revised international prognostic index (R-IPI) and cell-of-origin (COO). Tissue findings were validated in 233 DLBCL R-CHOP treated patients. Furthermore, within the blood of 140 R-CHOP treated patients immune-effector:checkpoint ratios were associated with differential interim-PET/CT+ve/-ve expression.

STEM education K-12: perspectives on integration

This commentary was stimulated by Yeping Li's first editorial (2014) citing one of the journal's goals as adding multidisciplinary perspectives to current studies of single disciplines comprising the focus of other journals. In this commentary I argue for a greater focus on STEM integration, with a more equitable representation of the four disciplines in studies purporting to advance STEM learning. The STEM acronym is often used in reference to just one of the disciplines, commonly science. Although the integration of STEM disciplines is increasingly advocated in the literature, studies that address multiple disciplines appear scant with mixed findings and inadequate directions for STEM advancement. Perspectives on how discipline integration can be achieved are varied, with reference to multidisciplinary, interdisciplinary, and transdisciplinary approaches adding to the debates. Such approaches include core concepts and skills being taught separately in each discipline but housed within a common theme; the introduction of closely linked concepts and skills from two or more disciplines with the aim of deepening understanding and skills; and the adoption of a transdisciplinary approach, where knowledge and skills from two or more disciplines are applied to real-world problems and projects with the aim of shaping the total learning experience. Research that targets STEM integration is an embryonic field with respect to advancing curriculum development and various student outcomes. For example, we still need more studies on how student learning outcomes arise not only from different forms of STEM integration but also from the particular disciplines that are being integrated. As noted in this commentary, it seems that mathematics learning benefits less than the other disciplines in programs claiming to focus on STEM integration. Factors contributing to this finding warrant more scrutiny. Likewise, learning outcomes for engineering within K-12 integrated STEM programs appear under-researched. This commentary advocates a greater focus on these two disciplines within integrated STEM education research. Drawing on recommendations from the literature, suggestions are offered for addressing the challenges of integrating multiple disciplines faced by the STEM community.

Novel synthesis of superparamagnetic Ni-Co-B nanoparticles and their effect on superconductor properties of MgB2

A new procedure for the preparation of amorphous Ni-Co-B nanoparticles is reported, with a detailed investigation of their morphology by X-ray diffraction and transmission electron microscopy, as well as their magnetic properties. Many factors, such as chemical composition, anisotropy, size and shape of the particles, were controlled through chemical synthesis, resulting in the control of morphological and magnetic properties of the nanoparticles. Controlling pH values with ethylenediamine and using sodium dodecyl sulfate surfactant lowered the size of the nanoparticles to below 10 nm. Such a small structure and chemical disorder in nanocrystalline materials lead to magnetic properties that are different from those in their bulk-sized counterparts. The obtained nanoparticles can be used for different purposes, from pharmaceutical applications to implementations in different materials technology. The focus of this research is the synthesis of Ni-Co-B nanoparticles in a new way and studying the reaction of Ni-Co-B nanoparticles with Mg and B precursors and their effect on MgB2 properties. New nanostructures are formed in the reaction of Ni-Co-B nanoparticles with Mg: Mg2Ni, Co2Mg and possibly Mg2Co.

Bio-inspired multifunctional metallic foams through the fusion of different biological solutions

Nature is a school for scientists and engineers. Inherent multiscale structures of biological materials exhibit multifunctional integration. In nature, the lotus, the water strider, and the flying bird evolved different and optimized biological solutions to survive. In this contribution, inspired by the optimized solutions from the lotus leaf with superhydrophobic self-cleaning, the water strider leg with durable and robust superhydrophobicity, and the lightweight bird bone with hollow structures, multifunctional metallic foams with multiscale structures are fabricated, demonstrating low adhesive superhydrophobic self-cleaning, striking loading capacity, and superior repellency towards different corrosive solutions. This approach provides an effective avenue to the development of water strider robots and other aquatic smart devices floating on water. Furthermore, the resultant multifunctional metallic foam can be used to construct an oil/water separation apparatus, exhibiting a high separation efficiency and long-term repeatability. The presented approach should provide a promising solution for the design and construction of other multifunctional metallic foams in a large scale for practical applications in the petro-chemical field. Optimized biological solutions continue to inspire and to provide design idea for the construction of multiscale structures with multifunctional integration. Inspired by the optimized biological solutions from the lotus leaf with superhydrophobic self-cleaning, the water strider leg with durable and robust superhydrophobicity, and the lightweight bird bone with hollow structures, multifunctional metallic foams with multiscale structures are fabricated, demonstrating low adhesive superhydrophobic self-cleaning, striking loading capacity, stable corrosion resistance, and oil/water separation.

Unusual RNA plant virus integration in the soybean genome leads to the production of small RNAs

Horizontal gene transfer (HGT) is known to be a major force in genome evolution. The acquisition of genes from viruses by eukaryotic genomes is a well-studied example of HGT, including rare cases of non-retroviral RNA virus integration. The present study describes the integration of cucumber mosaic virus RNA-1 into soybean genome. After an initial metatranscriptomic analysis of small RNAs derived from soybean, the de novo assembly resulted a 3029-nt contig homologous to RNA-1. The integration of this sequence in the soybean genome was confirmed by DNA deep sequencing. The locus where the integration occurred harbors the full RNA-1 sequence followed by the partial sequence of an endogenous mRNA and another sequence of RNA-1 as an inverted repeat and allowing the formation of a hairpin structure. This region recombined into a retrotransposon located inside an exon of a soybean gene. The nucleotide similarity of the integrated sequence compared to other Cucumber mosaic virus sequences indicates that the integration event occurred recently. We described a rare event of non-retroviral RNA virus integration in soybean that leads to the production of a double-stranded RNA in a similar fashion to virus resistance RNAi plants.