Recent Advances in the Development of Biomimetic Materials

: In this review, we focused on recent efforts in the design and development of materials with biomimetic properties. Innovative methods promise to emulate cell microenvironments and tissue functions, but many aspects regarding cellular communication, motility, and responsiveness remain to be explained. We photographed the state-of-the-art advancements in biomimetics, and discussed the complexity of a "bottom-up" artificial construction of living systems, with particular highlights on hydrogels, collagen-based composites, surface modifications, and three-dimensional (3D) bioprinting applications. Fast-paced 3D printing and artificial intelligence, nevertheless, collide with reality: How difficult can it be to build reproducible biomimetic materials at a real scale in line with the complexity of living systems? Nowadays, science is in urgent need of bioengineering technologies for the practical use of bioinspired and biomimetics for medicine and clinics

Retrotransposons Are the Major Contributors to the Expansion of the \u3ci\u3eDrosophila ananassae\u3c/i\u3e Muller F Element

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (\u3e18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5′ ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains

Azurin as a Protein Scaffold for a Low-coordinate Nonheme Iron Site with a Small-molecule Binding Pocket

The apoprotein of <i>Pseudomonas aeruginosa</i> azurin binds iron­(II) to give a 1:1 complex, which has been characterized by electronic absorption, Mössbauer, and NMR spectroscopies, as well as X-ray crystallography and quantum-chemical computations. Despite potential competition by water and other coordinating residues, iron­(II) binds tightly to the low-coordinate site. The iron­(II) complex does not react with chemical redox agents to undergo oxidation or reduction. Spectroscopically calibrated quantum-chemical computations show that the complex has high-spin iron­(II) in a pseudotetrahedral coordination environment, which features interactions with side chains of two histidines and a cysteine as well as the CO of Gly45. In the ⁵A₁ ground state, the <i>d</i>_<i>z</i>² orbital is doubly occupied. Mutation of Met121 to Ala leaves the metal site in a similar environment but creates a pocket for reversible binding of small anions to the iron­(II) center. Specifically, azide forms a high-spin iron­(II) complex and cyanide forms a low-spin iron­(II) complex

Azurin as a Protein Scaffold for a Low-coordinate Nonheme Iron Site with a Small-molecule Binding Pocket

The apoprotein of <i>Pseudomonas aeruginosa</i> azurin binds iron­(II) to give a 1:1 complex, which has been characterized by electronic absorption, Mössbauer, and NMR spectroscopies, as well as X-ray crystallography and quantum-chemical computations. Despite potential competition by water and other coordinating residues, iron­(II) binds tightly to the low-coordinate site. The iron­(II) complex does not react with chemical redox agents to undergo oxidation or reduction. Spectroscopically calibrated quantum-chemical computations show that the complex has high-spin iron­(II) in a pseudotetrahedral coordination environment, which features interactions with side chains of two histidines and a cysteine as well as the CO of Gly45. In the ⁵A₁ ground state, the <i>d</i>_<i>z</i>² orbital is doubly occupied. Mutation of Met121 to Ala leaves the metal site in a similar environment but creates a pocket for reversible binding of small anions to the iron­(II) center. Specifically, azide forms a high-spin iron­(II) complex and cyanide forms a low-spin iron­(II) complex

Azurin as a Protein Scaffold for a Low-coordinate Nonheme Iron Site with a Small-molecule Binding Pocket

The apoprotein of <i>Pseudomonas aeruginosa</i> azurin binds iron­(II) to give a 1:1 complex, which has been characterized by electronic absorption, Mössbauer, and NMR spectroscopies, as well as X-ray crystallography and quantum-chemical computations. Despite potential competition by water and other coordinating residues, iron­(II) binds tightly to the low-coordinate site. The iron­(II) complex does not react with chemical redox agents to undergo oxidation or reduction. Spectroscopically calibrated quantum-chemical computations show that the complex has high-spin iron­(II) in a pseudotetrahedral coordination environment, which features interactions with side chains of two histidines and a cysteine as well as the CO of Gly45. In the ⁵A₁ ground state, the <i>d</i>_<i>z</i>² orbital is doubly occupied. Mutation of Met121 to Ala leaves the metal site in a similar environment but creates a pocket for reversible binding of small anions to the iron­(II) center. Specifically, azide forms a high-spin iron­(II) complex and cyanide forms a low-spin iron­(II) complex

Fairness and accountability design needs for algorithmic support in high-stakes public sector decision-making

Calls for heightened consideration of fairness and accountability in algorithmically-informed public decisions—like taxation, justice, and child protection—are now commonplace. How might designers support such human values? We interviewed 27 public sector machine learning practitioners across 5 OECD countries regarding challenges understanding and imbuing public values into their work. The results suggest a disconnect between organisational and institutional realities, constraints and needs, and those addressed by current research into usable, transparent and ‘discrimination-aware’ machine learning—absences likely to undermine practical initiatives unless addressed. We see design opportunities in this disconnect, such as in supporting the tracking of concept drift in secondary data sources, and in building usable transparency tools to identify risks and incorporate domain knowledge, aimed both at managers and at the ‘street-level bureaucrats’ on the frontlines of public service. We conclude by outlining ethical challenges and future directions for collaboration in these high-stakes applications

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures

Abstract Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting

Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element.

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (&gt;18.7 Mb) in D. ananassae To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5' ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains