Integrating Biocatalysts into Metal-Organic Frameworks: Disentangling the Roles of Affinity, Molecular Weight, and Size.

The integration of biocatalysts within metal-organic frameworks (MOFs) is attracting growing interest due to its potential to both enhance biocatalyst stability and sustain biocatalyst activity in organic solvents. However, the factors that facilitate the post-synthetic infiltration of such large molecules into MOF pores remain unclear. This systematic study enabled the identification of the influence of biocatalyst molecular size, molecular weight and affinity on the uptake by an archetypal MOF, NU-1000.

Reversible Influence of Hemipiperazine Photochromism on the Early Development of Zebrafish Embryo.

This study explores the potential of controlling organismal development with light by using reversible photomodulation of activity in bioactive compounds. Specifically, our research focuses on plinabulin 1, an inhibitor of tubulin dynamics that contains a photochromic motif called hemipiperazine. The two isomeric forms, Z-1 and E-1, can partially interconvert with light, yet show remarkable thermal stability in darkness.

Caveolae disassemble upon membrane lesioning and foster cell survival.

Repair of lesions in the plasma membrane is key to sustaining cellular homeostasis. Cells maintain cytoplasmic as well as membrane-bound stores of repair proteins that can rapidly precipitate at the site of membrane lesions. However, little is known about the origins of lipids and proteins for resealing and repair of the plasma membrane.

transgenic line and single-cell transcriptomics reveal the origin of zebrafish intraspinal serotonergic neurons.

Sox transcription factors are crucial for vertebrate nervous system development. In zebrafish embryo, genes are expressed in neural progenitor cells and neurons of ventral spinal cord. Our recent study revealed that the loss of and function results in a significant decline of V2 subtype neurons (V2s).

Smuggling on the Nanoscale-Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo.

The efficient and biocompatible transfer of nucleic acids into mammalian cells for research applications or medical purposes is a long-standing, challenging task. Viral transduction is the most efficient transfer system, but often entails high safety levels for research and potential health impairments for patients in medical applications. Lipo- or polyplexes are commonly used transfer systems but result in comparably low transfer efficiencies.

Fat Grafts Show Higher Hypoxia, Angiogenesis, Adipocyte Proliferation, and Macrophage Infiltration than Flaps in a Pilot Mouse Study.

Background: Over 137,000 breast reconstructions are performed annually by American Society of Plastic Surgeons (ASPS) members. Vascularized flaps and avascular lipofilling each account for over 33,000 autologous reconstructions. Although clinical and experimental observations suggest biologic differences with diverging effects on locoregional tumor control, comparative animal models are lacking.

Phenotypic Discovery of Triazolo[1,5-]quinazolines as a First-In-Class Bone Morphogenetic Protein Amplifier Chemotype.

Phenotypic drug discovery (PDD) continues to fuel the research and development pipelines with first-in-class therapeutic modalities, but success rates critically depend on the quality of the underlying model system. Here, we employed a stem cell-based approach for the target-agnostic, yet pathway-centric discovery of small-molecule cytokine signaling activators to act as morphogens during development and regeneration. Unbiased screening identified triazolo[1,5-]quinazolines as a new-in-class in vitro and in vivo active amplifier of the bone morphogenetic protein (BMP) pathway.

Highly Fluorinated Peptide Probes with Enhanced In Vivo Stability for F-MRI.

A labeling strategy for in vivo F-MRI (magnetic resonance imaging) based on highly fluorinated, short hydrophilic peptide probes, is developed. As dual-purpose probes, they are functionalized further by a fluorophore and an alkyne moiety for bioconjugation. High fluorination is achieved by three perfluoro-tert-butyl groups, introduced into asparagine analogues by chemically stable amide bond linkages.

Loss of the Bardet-Biedl protein Bbs1 alters photoreceptor outer segment protein and lipid composition.

Primary cilia are key sensory organelles whose dysfunction leads to ciliopathy disorders such as Bardet-Biedl syndrome (BBS). Retinal degeneration is common in ciliopathies, since the outer segments (OSs) of photoreceptors are highly specialized primary cilia. BBS1, encoded by the most commonly mutated BBS-associated gene, is part of the BBSome protein complex.

Two plus one is almost three: a fast approximation for multi-view deconvolution.

Multi-view deconvolution is a powerful image-processing tool for light sheet fluorescence microscopy, providing isotropic resolution and enhancing the image content. However, performing these calculations on large datasets is computationally demanding and time-consuming even on high-end workstations. Especially in long-time measurements on developing animals, huge amounts of image data are acquired.

Methylmercury-induced hair cell loss requires hydrogen peroxide production and leukocytes in zebrafish embryos.

Hearing impairment and deafness is frequently observed as one of the neurological signs in patients with Minamata disease caused by methylmercury (MeHg) poisoning. Loss of hair cells in humans and animals is a consequence of MeHg poisoning. However, it is still not clear how MeHg causes hearing deficits.

Neuron-Radial Glial Cell Communication via BMP/Id1 Signaling Is Key to Long-Term Maintenance of the Regenerative Capacity of the Adult Zebrafish Telencephalon.

The central nervous system of adult zebrafish displays an extraordinary neurogenic and regenerative capacity. In the zebrafish adult brain, this regenerative capacity relies on neural stem cells (NSCs) and the careful management of the NSC pool. However, the mechanisms controlling NSC pool maintenance are not yet fully understood.

Behavior of the Antibacterial Peptide Cyclo[RRRWFW], Explored Using a 3-Hydroxychromone-Derived Fluorescent Amino Acid.

Labeling biomolecules with fluorescent labels is an established tool for structural, biochemical, and biophysical studies; however, it remains underused for small peptides. In this work, an amino acid bearing a 3-hydroxychromone fluorophore, 2-amino-3-(2-(furan-2-yl)-3-hydroxy-4-oxo-4H-chromen-6-yl)propanoic acid (FHC), was incorporated in a known hexameric antimicrobial peptide, cyclo[RRRWFW] (cWFW), in place of aromatic residues. Circular dichroism spectropolarimetry and antibacterial activity measurements demonstrated that the FHC residue perturbs the peptide structure depending on labeling position but does not modify the activity of cWFW significantly.

MondoA regulates gene expression in cholesterol biosynthesis-associated pathways required for zebrafish epiboly.

The glucose-sensing Mondo pathway regulates expression of metabolic genes in mammals. Here, we characterized its function in the zebrafish and revealed an unexpected role of this pathway in vertebrate embryonic development. We showed that knockdown of impaired the early morphogenetic movement of epiboly in zebrafish embryos and caused microtubule defects.

Pax6 organizes the anterior eye segment by guiding two distinct neural crest waves.

Cranial neural crest (NC) contributes to the developing vertebrate eye. By multidimensional, quantitative imaging, we traced the origin of the ocular NC cells to two distinct NC populations that differ in the maintenance of sox10 expression, Wnt signalling, origin, route, mode and destination of migration. The first NC population migrates to the proximal and the second NC cell group populates the distal (anterior) part of the eye.

Bone morphogenetic protein signaling regulates Id1-mediated neural stem cell quiescence in the adult zebrafish brain via a phylogenetically conserved enhancer module.

In the telencephalon of adult zebrafish, the inhibitor of DNA binding 1 (id1) gene is expressed in radial glial cells (RGCs), behaving as neural stem cells (NSCs), during constitutive and regenerative neurogenesis. Id1 controls the balance between resting and proliferating states of RGCs by promoting quiescence. Here, we identified a phylogenetically conserved cis-regulatory module (CRM) mediating the specific expression of id1 in RGCs.

Correction to: Gene duplication and functional divergence of the zebrafish otospiralin genes.

In the originally published article, the first names and family names of the authors were interchanged, hence not correct. The correct presentation of names is presented above.

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos.

This study evaluates the embryotoxicity of dithienylethene-modified peptides upon photoswitching, using 19 analogues based on the β-hairpin scaffold of the natural membranolytic peptide gramicidin S. We established an in vivo assay in two variations (with ex vivo and in situ photoisomerization), using larvae of the model organism and determined the toxicities of the peptides in terms of 50% lethal doses (LD). This study allowed us to: (i) demonstrate the feasibility of evaluating peptide toxicity with larvae at 3-4 days post fertilization, (ii) determine the phototherapeutic safety windows for all peptides, (iii) demonstrate photoswitching of the whole-body toxicity for the dithienylethene-modified peptides in vivo, (iv) re-analyze previous structure-toxicity relationship data, and (v) select promising candidates for potential clinical development.

Differential Nanoparticle Sequestration by Macrophages and Scavenger Endothelial Cells Visualized in Real-Time and at Ultrastructural Resolution.

Despite the common knowledge that the reticuloendothelial system is largely responsible for blood clearance of systemically administered nanoparticles, the sequestration mechanism remains a "black box". Using transgenic zebrafish embryos with cell type-specific fluorescent reporters and fluorescently labeled model nanoparticles (70 nm SiO), we here demonstrate simultaneous three-color imaging of intravenously injected nanoparticles, macrophages, and scavenger endothelial cells (SECs). The trafficking processes were further revealed at ultrastructural resolution by transmission electron microscopy.

Gene duplication and functional divergence of the zebrafish otospiralin genes.

Otospiralin (OTOSP) is a small protein of unknown function, expressed in fibrocytes of the inner ear and required for normal cochlear auditory function. Despite its conservation from fish to mammals, expression of otospiralin was only investigated in mammals. Here, we report for the first time the expression profile of OTOS orthologous genes in zebrafish (Danio rerio): otospiralin and si:ch73-23l24.

Functions of thioredoxin1 in brain development and in response to environmental chemicals in zebrafish embryos.

Thioredoxin is an evolutionarily conserved antioxidant protein that plays a crucial role for fundamental cellular processes and embryonic development. Growing evidence support that Thioredoxin influences cellular response to chemicals insults, particularly those accompanying oxidative stress. The mechanisms underlying the functions of Thioredoxin1 in the embryonic development under the environmental toxicant exposure remain, however, largely unexplored.

Straightforward access to biocompatible poly(2-oxazoline)-coated nanomaterials by polymerization-induced self-assembly.

We report the synthesis of poly(2-ethyl-2-oxazoline)-based (PEtOx) nanoobjects by polymerization-induced self-assembly (PISA). First, well-defined PEtOx macromolecular chain transfer agents were synthesized by cationic ring-opening polymerization and click chemistry. The photoinitiated PISA of 2-hydroxypropyl methacrylate mediated by these PEtOx produced nanoobjects spanning the full range of core-shell morphologies.

The HMG box transcription factors Sox1a and Sox1b specify a new class of glycinergic interneuron in the spinal cord of zebrafish embryos.

Specification of neurons in the spinal cord relies on extrinsic and intrinsic signals, which in turn are interpreted by expression of transcription factors. V2 interneurons develop from the ventral aspects of the spinal cord. We report here a novel neuronal V2 subtype, named V2s, in zebrafish embryos.

Oriented immobilization of a delicate glucose-sensing protein on silica nanoparticles.

Silica nanoparticles are widely used platform materials for the immobilization of proteins to realize applications in biomedicine and biotechnology. We here report on the use of a highly delicate protein for the systematic evaluation of routes for the surface modification of multifunctional silica nanoparticles. To investigate how surface immobilization methods affect the functionality of surface-bound proteins, we constructed a novel fusion protein, dubbed FlipHOB, that combines the glucose sensor protein FLIP with a variant of the commercially-available self-ligating Halo-tag.