The establishment of tissue axes is fundamental during embryonic development. In the Drosophila wing, the anterior/posterior (AP) and the dorsal/ventral (DV) compartment boundaries provide the basic coordinates around which the tissue develops. These boundaries arise as a result of two lineage decisions, the acquisition of posterior fate by the selector gene engrailed (en) and dorsal fate by the selector gene apterous (ap). While the en expression domain is set up during embryogenesis, ap expression begins only during early wing development. Thus, the correct establishment of the ap expression pattern relative to en must be tightly controlled. Here, we functionally investigate the transcriptional inputs integrated by the early ap enhancer (apE) and their requirement for correct boundary formation. Detailed mutational analyses using CRISPR/Cas revealed a role for apE in positioning the DV boundary relative to the AP boundary, with apE mutants often displaying mirror-image anterior wing duplications. We then designed and applied methods to accomplish tissue-specific enhancer disruption via dCas9 expression. This approach allowed us to dissect the spatiotemporal requirement for apE function, clarifying the mechanism by which apE misregulation leads to AP defects. Base-pair-resolution analyses of apE uncovered a single HOX-binding site essential for wing development that, when mutated, led to wingless flies. We demonstrated that the transcription factors Pointed (Pnt), Homothorax (Hth), and Grain (Grn) are required for apE function, and the HOX gene Antennapedia (Antp) contributes to early wing development. Together, our results provide a comprehensive molecular basis of early ap activation and the developmental consequences of its misregulation, shedding light on how compartmental boundaries are set up during development.

Implant-associated-infections against the background of multi-drug-resistance cause severe complications in orthopedic and trauma surgery and burden global healthcare. Equipment of implants with antibacterial coatings loaded by lytic bacteriophages (PHAG) are seen promising in this respect. Here, we report antibacterial polyelectrolyte multilayer (PEM) coatings functionalized by PHAG, which were deposited at model substrates and metallic implants by consecutive adsorption from solutions of poly-l-lactide-modified hyaluronic acid (DAC), ethylenediamino-cellulose (EDAC) or poly(ethyleneimine) (PEI) according to layer-by-layer technique. PHAG against Staphylococcus aureus (S. aureus) bacteria were bound at five- and six-layered PEM coatings of PEI/DAC or EDAC/DAC, respectively. PEM deposition and PHAG interaction were studied by FTIR and SFM. In-vivo antibacterial properties of PHAG/PEM coatings against S. aureus bacteria were evaluated using Galleria mellonella (G. mellonella) larvae infection model. PEM coatings of EDAC/DAC revealed far higher deposited polymer amounts compared to PEI/DAC and far more PHAG were bound at thicker EDAC/DAC compared to thinner PEI/DAC coatings. Higher relative released PHAG amount (40-80%) was found for thinner PEI/DAC coatings, while lower one (10-20%) for thicker EDAC/DAC coatings. In-vivo studies revealed survival rates >80% of uninfected G. mellonella larvae treated with uncoated and PEM/PHAG coated metallic implants, indicating biocompatibility of the used materials. Infected G. mellonella larvae showed survival rates of 33%-43% for metallic implants with PEM/PHAG coatings of EDAC/DAC, which were higher with statistical significance compared to uncoated controls (13%), indicating excellent antibacterial properties.

We report a straightforward methodology to access structurally well-defined hybrid assemblies of plasmonic and excitonic nanoparticles (NPs). The developed strategy is based on the incorporation of quantum dots (QDs) coated with zinc-sulfide shells into poly(ethylene glycol) (PEG) brushes at gold NP surfaces, without the necessity of incorporating specialized functional groups to drive the supracolloidal assembly. Based on control experiments involving PEGs with distinct polymeric architecture and Fourier-transform infrared spectroscopy analysis, we attribute the structure formation to attractive interactions between the QD surface and the monomeric repeat unit of the PEG brushes. This combination leads to short interparticle spacings and plasmon/exciton interactions, resulting in photoluminescence (PL) quenching upon assembly. However, using block-copolymers comprising a NP-adjacent spacer block in addition to a NP-remote PEG block, the distance between gold NPs and QDs can be controlled, which in turn affects the PL properties. The versatility of the structure-formation approach is demonstrated by the possibility of applying it to two distinct core/shell QDs (InP/ZnSe/ZnS and CdSe/CdS/ZnS). This offers new perspectives in the quest for efficient nanomaterial fabrication procedures.

MicroRNAs are small, highly conserved non-coding RNAs that negatively regulate mRNA translation and stability. In the brain, miRNAs contribute to neuronal development, synaptogenesis, and synaptic plasticity. MicroRNA 138-5p (miR-138-5p) controls inhibitory synaptic transmission in the hippocampus and is highly expressed in cerebellar excitatory neurons. However, its specific role in cerebellar synaptic transmission remains unknown. Here, we investigated excitatory transmission in the cerebellum of mice expressing a sponge construct that sequesters endogenous miR-138-5p. Mossy fibre stimulation-evoked EPSCs in granule cells were ∼40% larger in miR-138-5p sponge mice compared to controls. Furthermore, we observed larger miniature EPSC amplitudes, suggesting an increased number of functional postsynaptic AMPA receptors. High-frequency train stimulation revealed enhanced short-term depression following miR-138-5p downregulation. Together with computational modelling, this suggests a negative regulation of presynaptic release probability. Overall, our results demonstrate that miR-138-5p suppresses synaptic strength through pre- and postsynaptic mechanisms, providing a potentially powerful mechanism for tuning excitatory synaptic input into the cerebellum. KEY POINTS: MicroRNAs are powerful regulators of mRNA translation and control key cell biological processes including synaptic transmission, but their role in regulating synaptic function in the cerebellum has remained elusive. In this study, we investigated how microRNA-138-5p (miR-138-5p) modulates excitatory transmission at adult murine cerebellar mossy fibre to granule cell synapses. Downregulation of miR-138-5p enhances excitatory synaptic strength at the cerebellar input layer and increases short-term depression. miR-138-5p exerts its regulatory function through both pre- and postsynaptic mechanisms by negatively regulating release probability at mossy fibre boutons, as well as functional AMPA receptor numbers in granule cells. These findings provide insights into the role of miR-138-5p in the cerebellum and expand our understanding of microRNA-dependent control of excitatory synaptic transmission and short-term plasticity.

Near-infrared (NIR) controlled drug delivery systems have drawn a lot of attention throughout the past few decades due to the deep penetration depth and comparatively minor side effects of the stimulus. In this study, we introduce an innovative approach for gastric cancer treatment by combining photothermal infrared-sensitive gold nanorods (AuNRs) with a conjugated microporous polymer (CMP) to create a drug delivery system tailored for transporting the cytostatic drug 5-fluorouracil (5-FU). CMPs are fully conjugated networks with high internal surface areas that can be precisely tailored to the adsorption and transport of active compounds through the right choice of chemical functionalities. By incorporation of surfactant-stabilized AuNRs into the CMP synthesis in dimethylformamide (DMF) the surfactant shell is destabilized and subsequently replaced by the CMP. Particularly, low initial surfactant concentrations led to uniform distribution of the AuNRs in the polymer matrix. Importantly, the integrated AuNRs maintain their plasmonic properties, as was confirmed via electron energy loss spectroscopy. Therefore, the significant photothermal properties are translated to the hybrid material as shown in a proof-of-principle experiment. Further, in an approximated gastric environment, 5-FU release studies were conducted with and without NIR stimulus. Thereby it was observed that increased Brownian motion due to the NIR irradiation not only accelerates the release but also increases the total released amount by influencing the adsorption-desorption equilibrium. This remarkable level of control of the release process underlines the immense potential of this hybrid material for precise and targeted drug delivery.

Weak polyelectrolyte brushes represent a versatile class of responsive surface coatings. The adjustment of their charges by modifying the pH value and the salt content of the surrounding solution has a considerable effect on the elongation of the brush, the interaction between the chains, and the degree of swelling. Recent studies have extensively demonstrated the impact of singly charged cations through theoretical and experimental means. Analyses of the interaction between polyacids and multicharged cations remain underrepresented. Therefore, the influence of multivalent cations (Ca2+ and Ce3+) on the swelling behavior of poly(acrylic acid) (PAA) brushes is investigated as a function of salt concentration and pH. Swelling measurements show a behavior that differs significantly from the well-known case of monovalent cations. To elucidate this anomalous behavior, this study employs a combination of in situ spectroscopic ellipsometry, atomic force microscopy (AFM), and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). The investigations reveal a highly intricate interaction behavior, which can be ascribed to the multivalency of the cations utilized. The FTIR measurements indicate the impact of the cations on the pKa value of the brush and the dissociation behavior. This study provides insights into the charging properties of PAA brushes, highlighting the decisive additional influence of the valency of the cations in combination with their concentration. Multivalent ions have been observed to substitute for the protons of the carboxyl groups through an entropically driven process, resulting in degrees of dissociation, α > 0.5, even at a pH of 3, where PAA brushes are expected to be fully undissociated. This phenomenon leads to an increased degree of swelling at very low salt concentrations and a reduction at increasing ionic strength. Evidence was found for different types of ion/carboxylate coordination, with bridging coordination between the carboxyl groups of PAA and the cations.

Gold nanorods (GNRs) coated with SiO2 are functionalized through thermally initiated free-radical thiol-ene click reactions, which couple vinyl groups on the SiO2 surface with thiols to form thioethers. This method of functionalization is developed as an alternative approach to thiolate functionalization of the gold surface. GNRs are synthesized using cetyltrimethylammonium bromide (CTAB), which is challenging to displace with thiols in high yield. In this work, a shell of SiO2 is instead deposited on the outer surface of the GNRs, which also maintains colloidal stability. A reaction with a vinyl silane then prepares the outer surface of the SiO2 shells for subsequent thiol-ene click reactions with five thiols that are selected to represent variations in structure and functional groups, including aliphatic and aromatic structures and acids and bases, demonstrating the versatility of the reaction. The SiO2 shell is initially 17 nm thick and further grows to 20 nm when functionalized with vinyl groups. Deposition of vinyl groups and the formation of thioethers are confirmed by Fourier-transform infrared (FTIR) spectroscopy and time-of-flight secondary ion mass spectrometry (ToF-SIMS). While FTIR spectroscopy is well-known for characterizing the surface of nanoparticles, ToF-SIMS has been applied less for this purpose and strongly complements analysis by FTIR spectroscopy.

Repetitive synaptic stimulation can induce different forms of synaptic plasticity but may also limit the robustness of synaptic transmission by exhausting key resources. Little is known about how synaptic transmission is stabilized after high-frequency stimulation. In the present study, we observed that tetanic stimulation of the Drosophila neuromuscular junction (NMJ) decreases quantal content, release-ready vesicle pool size and synaptic vesicle density for minutes after stimulation. This was accompanied by a pronounced increase in quantal size. Interestingly, action potential-evoked synaptic transmission remained largely unchanged. EPSC amplitude fluctuation analysis confirmed the post-tetanic increase in quantal size and the decrease in quantal content, suggesting that the quantal size increase counteracts release depression to maintain evoked transmission. The magnitude of the post-tetanic quantal size increase and release depression correlated with stimulation frequency and duration, indicating activity-dependent stabilization of synaptic transmission. The post-tetanic quantal size increase persisted after genetic ablation of the glutamate receptor subunits GluRIIA or GluRIIB, and glutamate receptor calcium permeability, as well as blockade of postsynaptic calcium channels. By contrast, it was strongly attenuated by pharmacological or presynaptic genetic perturbation of the GTPase dynamin. Similar observations were made after inhibition of the H+-ATPase, suggesting that the quantal size increase is presynaptically driven. Additionally, dynamin and H+-ATPase perturbation resulted in a post-tetanic decrease in evoked amplitudes. Finally, we observed an increase in synaptic vesicle diameter after tetanic stimulation. Thus, a presynaptically-driven quantal size increase, likely mediated by larger synaptic vesicles, counterbalances post-tetanic release depression, thereby conferring robustness to synaptic transmission on the minute time scale. KEY POINTS: Many synapses transmit robustly after sustained activity despite the limitation of key resources, such as release-ready synaptic vesicles. We report robust synaptic transmission after sustained high-frequency stimulation of the Drosophila neuromuscular junction despite a reduction in release-ready vesicle number. An increased postsynaptic response to individual vesicles, likely driven by an increase in vesicle size due to endocytosis defects, stabilizes synaptic efficacy for minutes after sustained activity. Our study provides novel insights into the mechanisms governing synaptic stability after sustained neural activity.

The infestation of tissue after implantation is a major problem as a bacterial biofilm can form on the surface of the implants, leading to implant-associated infections (IAIs). One approach to prevent such IAI is to apply antibacterial coatings consisting of polyelectrolyte multilayers (PEM) and bacteriophages (PHAGs). PEM were constructed by alternately adsorbing oppositely charged polyelectrolytes on a substrate according to the layer-by-layer concept. Poly(ethylenimine) (PEI) was used as the cationic polyelectrolyte, and a graft polymer of hyaluronic acid and poly(l-lactide) (DAC) was used as the anionic polyelectrolyte. Comparing PEM-5 (PEI/DAC/PEI/DAC/PEI) and PEM-6 (PEI/DAC/PEI/DAC/PEI/DAC), a higher amount of PHAG was bound to PEM-5 with cationic surface charge, which was detected by atomic force microscopy (AFM) measurements and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The binding of PHAG to the PEM is suggested to be based on electrostatic interactions between the anionic capsid proteins of PHAG and the outermost PEM surface. For antibacterial tests, PEM-5 and PEM-6 each with and without contact to PHAG were deposited at agar plates and infected with bacteria. For the coatings consisting of PEM and PHAG, a significant eradicative effect toward bacteria was obtained, while the pure PEM coatings showed no eradication, which proves the dominant antibacterial contribution originated by PHAG.

Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies1, which involve human-specific mechanisms2-5 that cannot be directly studied in animal models. Here, to explore the emergence and consequences of TDP-43 pathologies, we generated induced pluripotent stem cell-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors6. Single-cell transcriptomics and comparison to independent neural stem cells7 showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks (which we designate iNets). Neuronal and glial maturation in iNets was similar to that of cortical organoids8. Overexpression of wild-type TDP-43 in a minority of neurons within iNets led to progressive fragmentation and aggregation of the protein, resulting in a partial loss of function and neurotoxicity. Single-cell transcriptomics revealed a novel set of misregulated RNA targets in TDP-43-overexpressing neurons and in patients with TDP-43 proteinopathies exhibiting a loss of nuclear TDP-43. The strongest misregulated target encoded the synaptic protein NPTX2, the levels of which are controlled by TDP-43 binding on its 3' untranslated region. When NPTX2 was overexpressed in iNets, it exhibited neurotoxicity, whereas correcting NPTX2 misregulation partially rescued neurons from TDP-43-induced neurodegeneration. Notably, NPTX2 was consistently misaccumulated in neurons from patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TDP-43 pathology. Our work directly links TDP-43 misregulation and NPTX2 accumulation, thereby revealing a TDP-43-dependent pathway of neurotoxicity.

Intrinsically disordered proteins (IDPs) play an important role in molecular biology and medicine because their induced folding can lead to so-called conformational diseases, where β-amyloids play an important role. Still, the molecular folding process into the different substructures, such as parallel/antiparallel or extended β-sheet/crossed β-sheet is not fully understood. The recombinant spider silk protein eADF4(Cx) consisting of repeating modules C, which are composed of a crystalline (pep-c) and an amorphous peptide sequence (pep-a), can be used as a model system for IDP since it can assemble into similar structures. In this work, blend films of the pep-c and pep-a sequences were investigated to modulate the β-sheet formation by varying the molar fraction of pep-c and pep-a. Dichroic Fourier-transform infrared spectroscopy (FTIR), circular dichroism, spectroscopic ellipsometry, atomic force microscopy, and IR nanospectroscopy were used to examine the secondary structure, the formation of parallel and antiparallel β-sheets, their orientation, and the microscopic roughness and phase formation within peptide blend films upon methanol post-treatment. New insights into the formation of filament-like structures in these silk blend films were obtained. Filament-like structures could be locally assigned to β-sheet-rich structures. Further, the antiparallel or parallel character and the orientation of the formed β-sheets could be clearly determined. Finally, the ideal ratio of pep-a and pep-c sequences found in the fibroin 4 of the major ampullate silk of spiders could also be rationalized by comparing the blend and spider silk protein systems.

The literature lacks established concrete parameters for assigning grafted chain regimes. In this context, dichroic in situ attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and in situ ellipsometry were used complementarily, offering new opportunities for conformational analysis of end-grafted polymer chains. Especially polymer chain orientation was studied as a new parameter, among others, for proper chain regime assignment in this report. Alkyne-functionalized poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) with a molecular weight of 49.8 kg/mol and a contour length of around 80 nm was grafted to self-assembled monolayers bearing triazole end groups as reported. Different chain regimes were generated by using three different grafting densities. ATR-FTIR spectroscopy based on the ν(C═O) stretching vibration at around 1728 cm-1 provided a new direct approach to determine the GD of polymer chains. Significant shifts in the position of the ν(C═O) band comparing dry and wet states were observed, caused by increased hydrogen bonding interactions between PDMAEMA and water. Finally, the averaged orientation of PDMAEMA chains along the z-axis was determined using dichroic ATR-FTIR spectroscopy based on the dichroic ratios of the ν(C═O) band and molecular order parameters SZ,MOL calculated thereof. High SZ,MOL values were found for the wet state compared to the dry state, confirming that all GD PDMAEMA samples are in the brush regime in the swollen state.

Bayesian Active Learning (BAL) is an efficient framework for learning the parameters of a model, in which input stimuli are selected to maximize the mutual information between the observations and the unknown parameters. However, the applicability of BAL to experiments is limited as it requires performing high-dimensional integrations and optimizations in real time. Current methods are either too time consuming, or only applicable to specific models. Here, we propose an Efficient Sampling-Based Bayesian Active Learning (ESB-BAL) framework, which is efficient enough to be used in real-time biological experiments. We apply our method to the problem of estimating the parameters of a chemical synapse from the postsynaptic responses to evoked presynaptic action potentials. Using synthetic data and synaptic whole-cell patch-clamp recordings, we show that our method can improve the precision of model-based inferences, thereby paving the way towards more systematic and efficient experimental designs in physiology.

Like multiblock copolymers, spider silk proteins are built of repetitive sequence motives. One prominent repetitive motif is based on the consensus sequence of spidroin 4 of the spider Araneus diadematus ADF4. The number x of the repeating sequence motives (C) determines the molecular weight of the recombinant ADF4-based, engineered spider silk protein denoted as eADF4(Cx). eADF4(Cx) can be used as a model for intrinsically disordered proteins (IDP) and to elucidate their folding. Herein, the influence of the variation of the sequence motive repeating number x (x = 1, 2, 4, 8, 16) on the protein folding within eADF4(Cx) films was investigated. eADF4(Cx) films were cast from 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) solutions onto planar silicon model substrates, revealing mainly helical or random coil structure. Upon treatment with methanol vapor (ptm), the formation of crystalline β-sheets was triggered. Dichroic Fourier-transform infrared (FTIR) spectroscopy, circular dichroism, spectroscopic ellipsometry, atomic force microscopy, grazing-incidence small-angle X-ray scattering (GISAXS), grazing-incidence wide-angle X-ray scattering (GIWAXS), and electrokinetic and contact angle measurements were used to get information concerning the secondary structure and folding kinetics, orientation of β-sheets, the ratio of parallel/antiparallel β-sheets, domain sizes and distributions, surface topography, surface potential, hydrophobicity and the film integrity under water. Significant differences in the final β-sheet content, the share of antiparallel β-sheet structures, film integrity, surface potential, and isoelectric points between eADF4(Cx) with x = 1, 2 and eADF4(Cx) with x = 4, 8, 16 gave new insights in the molecular weight-dependent structure formation and film properties of IDP systems. GISAXS and kinetic measurements confirmed a relation between β-sheet crystal growth rate and final β-sheet crystal size. Further, competing effects of reduced diffusibility hindering accelerated crystal growth and enhanced backfolding promoting accelerated crystal growth with increasing molecular weight were discussed.

The pKa values of propanolamine hydrochloride (PAMH) and poly(allylamine hydrochloride) (PAAMH) in concentrated solutions were determined by both Fourier transform infrared spectroscopy (FT-IR) titration and classical potentiometric (POT) titration and compared. Starting with the respective fully protonated forms PAMH and PAAMH and increasing the pH value by sodium hydroxide addition in situ attenuated total reflection FT-IR (ATR FT-IR) spectra on PAMH and PAAMH solutions show the variation of diagnostic infrared (IR) bands. From the decrease of the most intense δ(NH3+) band the dissociation process of the NH3+ groups could be followed. Thereby, from the respective normalized band area A the dissociation degree αIR of the ammonium groups could be determined. Plotting pH versus αIR and fitting this curve by a modified Henderson-Hasselbalch function pH = pKa + B log (αIR/1 - αIR) the parameters pKa and cooperativity factor B were obtained. pKa values from FT-IR titration were qualitatively in line with respective pKa values from POT titration. Quantitative systematic pKa deviations between polyelectrolyte (PEL) and respective monoelectrolyte and the tentative effects of PEL molecular weight, ambient ionic strength, and titration concept (FT-IR and POT) are discussed based on classical models of weak PEL.

Amyloid β peptide can aggregate into thin β-sheet fibrils or plaques deposited on the extracellular matrix, which is the hallmark of Alzheimer's disease. Multifunctional macromolecular structures play an important role in inhibiting the aggregate formation of amyloidogenic materials and thus are promising candidates with antiamyloidogenic characteristics for the development of next-generation therapeutics. In this study, we evaluate how small differences in the dendritic topology of these structures influence their antiamyloidogenic activity by the comparison of "perfectly dendritic" and "pseudodendritic" macromolecules, both decorated with mannose units. Their compactness, the position of surface units, and the size of glyco-architectures influence their antiamyloidogenic activity against Aβ 40, a major component of amyloid plaques. For the advanced analysis of the aggregation of the Aβ peptide, we introduce asymmetric flow field flow fractionation as a suitable method for the quantification of large and delicate structures. This alternative method focuses on the quantification of complex aggregates of Aβ 40 and glycodendrimer/glyco-pseudodendrimer over different time intervals of incubation, showing a good correlation to ThT assay and CD spectroscopy results. Kinetic studies of the second-generation glyco-pseudodendrimer revealed maximum inhibition of Aβ 40 aggregates, verified with atomic force microscopy. The second-generation glyco-pseudodendrimer shows the best antiamyloidogenic properties confirming that macromolecular conformation in combination with optimal functional group distribution is the key to its performance. These molecular properties were validated and confirmed by molecular dynamics simulation.

Chromatin insulators have been proposed to play an important role in chromosome organization and local regulatory interactions. In Drosophila , one of these insulators is known as Wari. It is located immediately downstream of the 3' end of the white transcription unit. Wari has been proposed to interact with the white promoter region, thereby facilitating recycling of the RNA polymerase machinery. We have tested this model by deleting the Wari insulator at the endogenous white locus and could not detect a significant effect on eye pigmentation.

Photocatalytic coatings represent dynamic light switchable interfaces and offer applications in industrial and even personal waste water treatment concerning pollutant removal. In this framework, nanoparticular suspensions and scalable coatings composed of TiO2 and weak polyelectrolytes (PE) were generated and studied concerning photoacidity and photodegradation applying UV light at a wavelength close to the band gap of TiO2. The TiO2 modifications anatase and rutile and anionic poly(acrylic acid) (PAA), cationic poly(allylamine) (PAH), and ampholytic poly(dehydroalanine-graft-phosphonylacrylamide) (PDHAG) were utilized at germanium model substrates. Colloid, interfacial, and photocatalytic properties were investigated by potentiometry, dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and scanning force microscopy (SFM). Upon UV illumination at 365 nm, all PE/anatase suspensions showed a significant pH decrease from pH = 6.00 down to pH = 5.27 and, partly, chemical changes within the PE fraction, while PE/rutile suspensions did not show such a pH drop. In comparison to the suspensions, PE/anatase coatings revealed less photoacidic properties but significant photocatalytic degradation of the bound PE, while this effect was absent in the case of PE/rutile samples. In application studies, acetate or anti-inflammatory drug flufenamic acid loaded into PE/anatase coatings could be significantly degraded upon UV illumination.

Synaptic proteins and synaptic transmission are under homeostatic control, but the relationship between these two processes remains enigmatic. Here, we systematically investigated the role of E3 ubiquitin ligases, key regulators of protein degradation-mediated proteostasis, in presynaptic homeostatic plasticity (PHP). An electrophysiology-based genetic screen of 157 E3 ligase-encoding genes at the Drosophila neuromuscular junction identified thin , an ortholog of human tripartite motif-containing 32 ( TRIM32 ), a gene implicated in several neurological disorders, including autism spectrum disorder and schizophrenia. We demonstrate that thin functions presynaptically during rapid and sustained PHP. Presynaptic thin negatively regulates neurotransmitter release under baseline conditions by limiting the number of release-ready vesicles, largely independent of gross morphological defects. We provide genetic evidence that thin controls release through dysbindin , a schizophrenia-susceptibility gene required for PHP. Thin and Dysbindin localize in proximity within presynaptic boutons, and Thin degrades Dysbindin in vitro. Thus, the E3 ligase Thin links protein degradation-dependent proteostasis of Dysbindin to homeostatic regulation of neurotransmitter release.