Domain Exchange Research Articles

The Autonomous Fusion Activity of Human Cytomegalovirus Glycoprotein B Is Regulated by Its Carboxy-Terminal Domain.

The human cytomegalovirus (HCMV) glycoprotein B (gB) is the viral fusogen required for entry into cells and for direct cell-to-cell spread of the virus. We have previously demonstrated that the exchange of the carboxy-terminal domain (CTD) of gB for the CTD of the structurally related fusion protein G of the vesicular stomatitis virus (VSV-G) resulted in an intrinsically fusion-active gB variant (gB/VSV-G). In this present study, we employed a dual split protein (DSP)-based cell fusion assay to further characterize the determinants of fusion activity in the CTD of gB. We generated a comprehensive library of gB CTD truncation mutants and identified two mutants, gB-787 and gB-807, which were fusion-competent and induced the formation of multinucleated cell syncytia in the absence of other HCMV proteins. Structural modeling coupled with site-directed mutagenesis revealed that gB fusion activity is primarily mediated by the CTD helix 2, and secondarily by the recruitment of cellular SH2/WW-domain-containing proteins. The fusion activity of gB-807 was inhibited by gB-specific monoclonal antibodies (MAbs) targeting the antigenic domains AD-1 to AD-5 within the ectodomain and not restricted to MAbs directed against AD-4 and AD-5 as observed for gB/VSV-G. This finding suggested a differential regulation of the fusion-active conformational state of both gB variants. Collectively, our findings underscore a pivotal role of the CTD in regulating the fusogenicity of HCMV gB, with important implications for understanding the conformations of gB that facilitate membrane fusion, including antigenic structures that could be targeted by antibodies to block this essential step in HCMV infection.

Characterization of a marine endolysin LysVPB against Vibrio parahaemolyticus

Currently, there is an urgent to develop safe and environmentally friendly alternatives to antibiotics for combating Vibrio parahaemolyticus. Endolysins are considered promising antibacterial agents due to their desirable range of action and ability to deal with antibiotic-resistant bacteria. While numerous Vibrio phages have been identified, the research on their endolysins is still in its infancy. In this study, a novel endolysin called LysVPB was cloned and expressed in Pichia pastoris. Phylogenetic analysis revealed that LysVPB bears little resemblance to other known endolysins, highlighting its unique nature. Homology modeling identified a putative calcium-binding site in LysVPB. The recombinant LysVPB achieved a lytic activity of 64.8 U/mL and had a molecular weight of approximately 17 kDa. LysVPB exhibited enhanced efficacy at pH 9.0, with 60 % of its maximum activity observed within the broad pH range of 6.0–10.0. The catalytic efficiency of LysVPB peaked at 30 °C but significantly declined beyond 50 °C. Ba2+, Co2+, and Cu2+ showed inhibitory effects on the activity of LysVPB, while Ca2+ can boost it to 126.8 %. Furthermore, LysVPB exhibited satisfactory efficacy against strains of V. parahaemolyticus. LysVPB is an innovative phage lysin with good characteristics that are specific to certain hosts. The modular nature of LysVPB allows for efficient domain exchange with alternative lysins as antimicrobial components and fusion with antimicrobial peptides. This opens up possibilities for engineering chimeric lysins in a broader range of target hosts with high antimicrobial effectiveness and strong activity under physiological conditions.

Differential conformational dynamics in two type-A RNA-binding domains drive the double-stranded RNA recognition and binding.

Trans-activation response (TAR) RNA-binding protein (TRBP) has emerged as a key player in the RNA interference pathway, wherein it binds to different pre-microRNAs (miRNAs) and small interfering RNAs (siRNAs), each varying in sequence and/or structure. We hypothesize that TRBP displays dynamic adaptability to accommodate heterogeneity in target RNA structures. Thus, it is crucial to ascertain the role of intrinsic and RNA-induced protein dynamics in RNA recognition and binding. We have previously elucidated the role of intrinsic and RNA-induced conformational exchange in the double-stranded RNA-binding domain 1 (dsRBD1) of TRBP in shape-dependent RNA recognition. The current study delves into the intrinsic and RNA-induced conformational dynamics of the TRBP-dsRBD2 and then compares it with the dsRBD1 study carried out previously. Remarkably, the two domains exhibit differential binding affinity to a 12-bp dsRNA owing to the presence of critical residues and structural plasticity. Furthermore, we report that dsRBD2 depicts constrained conformational plasticity when compared to dsRBD1. Although, in the presence of RNA, dsRBD2 undergoes induced conformational exchange within the designated RNA-binding regions and other residues, the amplitude of the motions remains modest when compared to those observed in dsRBD1. We propose a dynamics-driven model of the two tandem domains of TRBP, substantiating their contributions to the versatility of dsRNA recognition and binding.

Evolution of Digital Health and Exploration of Patented Technologies (2017-2021): Bibliometric Analysis.

The significant impact of digital health emerged prominently during the COVID-19 pandemic. Despite this, there is a paucity of bibliometric analyses focusing on technologies within the field of digital health patents. Patents offer a wealth of insights into technologies, commercial prospects, and competitive landscapes, often undisclosed in other publications. Given the rapid evolution of the digital health industry, safeguarding algorithms, software, and advanced surgical devices through patent systems is imperative. The patent system simultaneously acts as a valuable repository of technological knowledge, accessible to researchers. This accessibility facilitates the enhancement of existing technologies and the advancement of medical equipment, ultimately contributing to public health improvement and meeting public demands. The primary objective of this study is to gain a more profound understanding of technology hotspots and development trends within the field of digital health. Using a bibliometric analysis methodology, we assessed the global technological output reflected in patents on digital health published between 2017 and 2021. Using Citespace5.1R8 and Excel 2016, we conducted bibliometric visualization and comparative analyses of key metrics, including national contributions, institutional affiliations, inventor profiles, and technology topics. A total of 15,763 digital health patents were identified as published between 2017 and 2021. The China National Intellectual Property Administration secured the top position with 7253 published patents, whereas Koninklijke Philips emerged as the leading institution with 329 patents. Notably, Assaf Govari emerged as the most prolific inventor. Technology hot spots encompassed categories such as "Medical Equipment and Information Systems," "Image Analysis," and "Electrical Diagnosis," classified by Derwent Manual Code. A patent related to the technique of receiving and transmitting data through microchips garnered the highest citation, attributed to the patentee Covidien LP. The trajectory of digital health patents has been growing since 2017, primarily propelled by China, the United States, and Japan. Applications in health interventions and enhancements in surgical devices represent the predominant scenarios for digital health technology. Algorithms emerged as the pivotal technologies protected by patents, whereas techniques related to data transfer, storage, and exchange in the digital health domain are anticipated to be focal points in forthcoming basic research.

Blockchain in Real Estate: A Comprehensive Review

Abstract: This review paper meticulously examines the transformative impact of blockchain technology within the real estate sector. The investigation focuses on the revolutionary changes instigated by blockchain, particularly concerning property ownership and title management. Noteworthy aspects include the establishment of secure ledgers for titles and the integration of smart contracts as pivotal instruments for automating and securing transactions. The insightful examination amplifies to the investigation of tokenization as a component to democratize genuine domain speculations, permitting for fragmentary proprietorship and extending the range of venture opportunities. Critical consideration is devoted to dismembering the productivity picks up characteristic in genuine domain exchanges encouraged by the arrangement of smart contracts. This key execution diminishes dependence on ordinary mediators, streamlining the generally exchange lifecycle. The permanent characteristics of property records on the blockchain are unpredictably inspected, highlighting their urgent part in upgrading information judgment, moderating extortion dangers, and building up an faithful store of solid data. The scholastic investigation amplifies to the application of blockchain in optimizing property administration forms, particularly through the computerized execution of rental understandings.

Genetic mechanisms underlying the structural elaboration and dissemination of viral internal ribosomal entry sites.

Viral internal ribosomal entry sites (IRESs) form several classes that use distinct mechanisms to mediate end-independent initiation of translation. The origin of viral IRESs is a longstanding question. The simplest IRESs comprise tandem pseudoknots and occur in the intergenic region (IGR) of Dicistroviridae genomes (order Picornavirales ). Larger IGR IRESs contain additional elements that determine specific properties such as binding to the head of the ribosoma l 40S subunit. Metagenomic analyses reported here identified novel groups of structurally distinct IGR-like IRESs. The smallest of these (∼120nt long) comprise three pseudoknots and bind directly to the ribosomal P site. Others are up to 260nt long: insertions occurred at specific loci, possibly reflecting non-templated nucleotide insertion during replication. Various groups can be arranged in order, differing by the cumulative addition of single structural elements, suggesting an accretion mechanism for the structural elaboration of IRESs. Identification of chimeric IRESs implicates recombinational exchange of domains as a second mechanism for the diversification of IRES structure. Recombination likely also accounts for the presence of IGR-like IRESs at the 5'-end of some dicistrovirus-like genomes (e.g. Hangzhou dicistrovirus 3) and in the RNA genomes of Tombusviridae (order Tolivirales ), Marnaviridae (order Picornavirale s), and the 'Ripiresk' picorna-like clade (order Picornavirale s).

Helicity-flip transitions and the t-dependence of exclusive photoproduction of rho meson

We calculate the differential cross section dσ/dt for the diffractive photoproduction process γp → ρp and compare our results with experimental data. Our model is based on two-gluon exchange in the nonperturbative domain. We take into account both helicity conserving and often neglected helicity-flip amplitudes in the γ → V transition, which can contribute at finite t. The shape of the differential cross section as well as the role of helicity-flip processes is strongly related to the dependence of the unintegrated gluon distribution on transverse momenta in the nonperturbative region.

Molecular basis for proofreading by the unique exonuclease domain of Family-D DNA polymerases

Replicative DNA polymerases duplicate entire genomes at high fidelity. This feature is shared among the three domains of life and is facilitated by their dual polymerase and exonuclease activities. Family D replicative DNA polymerases (PolD), found exclusively in Archaea, contain an unusual RNA polymerase-like catalytic core, and a unique Mre11-like proofreading active site. Here, we present cryo-EM structures of PolD trapped in a proofreading mode, revealing an unanticipated correction mechanism that extends the repertoire of protein domains known to be involved in DNA proofreading. Based on our experimental structures, mutants of PolD were designed and their contribution to mismatch bypass and exonuclease kinetics was determined. This study sheds light on the convergent evolution of structurally distinct families of DNA polymerases, and the domain acquisition and exchange mechanism that occurred during the evolution of the replisome in the three domains of life.

Pulse energy exchange of vector solitons in a fiber laser

The energy exchange between orthogonal polarization components is crucial for the build-up of vector solitons (VSs). Unlike previous observations of energy exchange in the frequency domain, our experiments analyzed pulse energy flows in the time domain. We provide evidence to demonstrate the influence of the four-wave mixing (FWM) and cross-phase modulation (XPM) effect on VSs build-up in passive mode-locked fiber lasers through a perspective of pulse energy exchange. The results indicate that the energy exchange of PRVS caused by FWM and XPM is stronger than that of PLVS. The liner energy exchange caused by the birefringence of fiber and PC influences the period of energy exchange. After stabilization, the intra-cavity energy evolution period is one roundtrip for PLVS while serval roundtrips for PRVS. In the future, we can achieve PLVS by adjusting the linear energy exchange through cavity birefringence, thereby meeting the industrial demand for stable and uniform pulse trains.

Geometrical representation of subshifts for primitive substitutions

Abstract For any primitive substitution whose Perron eigenvalue is a Pisot unit, we construct a domain exchange that is measurably conjugate to the subshift. Additionally, we give a condition for the subshift to be a finite extension of a torus translation. For the particular case of weakly irreducible Pisot substitutions, we show that the subshift is either a finite extension of a torus translation or its eigenvalues are roots of unity. Furthermore, we provide an algorithm to compute eigenvalues of the subshift associated with any primitive pseudo-unimodular substitution.

Improving Access to Medical Information for Multilingual Patients using Pipelined Ensemble Average based Machine Translation

Machine translation has shown potential in improving access to medical information and healthcare services for multilingual patients. This research aims to enhance machine translation accuracy in the medical field, specifically for translating from Hindi to English. The study introduces a new approach that dynamically allocates decoding parameters using regression models, overcoming the limitations of fixed parameters in the decoder. A comprehensive dataset is created to address limited data availability, enabling regression models to predict optimal pruning parameters. The main motivation for the study is the introduction of a regression method for optimizing pruning parameters, which is a novel approach in this context. The proposed approach outperforms existing methods, achieving improved translation accuracy. Standard metrics such as the BLEU score are used to evaluate translations. Ensemble average and pipeline approaches further enhance performance. The improved performance of the proposed models can be attributed to the ensemble of diverse models (Extra Trees, LightGBM, XGBoost, and Random Forest) that employ various techniques to reduce overfitting, enhance prediction accuracy, and improve translation by correcting prediction errors. The study contributes to facilitating the translation and sharing of medical literature, promoting collaboration and knowledge exchange across languages. The research demonstrates the effectiveness of the regression method for optimizing pruning parameters in machine translation, leading to improved translation accuracy in the medical field. The proposed models offer promising results, paving the way for enhanced machine translation systems and promoting collaboration and knowledge exchange in the medical domain. The source code is available at https://huggingface.co/debajyoty/statistical-regression-Based-MT/tree/main/Statistical-Regression-SMT.

Biosensor Guided Polyketide Synthases Engineering for Optimization of Domain Exchange Boundaries

Type I modular polyketide synthases (PKSs) are multi-domain enzymes functioning like assembly lines. Many engineering attempts have been made for the last three decades to replace, delete and insert new functional domains into PKSs to produce novel molecules. However, inserting heterologous domains often destabilize PKSs, causing loss of activity and protein misfolding. To address this challenge, here we develop a fluorescence-based solubility biosensor that can quickly identify engineered PKSs variants with minimal structural disruptions. Using this biosensor, we screen a library of acyltransferase (AT)-exchanged PKS hybrids with randomly assigned domain boundaries, and we identify variants that maintain wild type production levels. We then probe each position in the AT linker region to determine how domain boundaries influence structural integrity and identify a set of optimized domain boundaries. Overall, we have successfully developed an experimentally validated, high-throughput method for making hybrid PKSs that produce novel molecules.

Discontinuous Galerkin method for hybrid-dimensional fracture models of two-phase flow

In this paper, we present a discontinuous Galerkin (DG) method for the simulation of incompressible and immiscible two-phase flow in fractured porous media with capillary pressure. The hybrid-dimensional fracture models are considered in which fractures are treated as (d−1)-dimensional interfaces in the d-dimensional domain and fluid exchange between fractures and surrounding matrix is taken into account. The approximation schemes combining the DG method with the fully implicit backward Euler time discretization are formulated for models with a single fracture and intersecting fractures network, and the stability and unique solvability are established. Optimal error estimates in the discrete H1-norm for saturation and pressure are derived. Numerical experiments in two-dimensional geometry are conducted to verify the accuracy of our theoretical analysis. In addition to the backward Euler formulation, we also implement the algorithm with a kind of conventional IMplicit Pressure Explicit Saturation (IMPES) method.

Expanding Extender Substrate Selection for Unnatural Polyketide Biosynthesis by Acyltransferase Domain Exchange within a Modular Polyketide Synthase

Modular polyketide synthases (PKSs) are polymerases that employ α-carboxyacyl-CoAs as extender substrates. This enzyme family contains several catalytic modules, where each module is responsible for a single round of polyketide chain extension. Although PKS modules typically use malonyl-CoA or methylmalonyl-CoA for chain elongation, many other malonyl-CoA analogues are used to diversify polyketide structures in nature. Previously, we developed a method to alter an extension substrate of a given module by exchanging an acyltransferase (AT) domain while maintaining protein folding. Here, we report in vitro polyketide biosynthesis by 13 PKSs (the wild-type PKS and 12 AT-exchanged PKSs with unusual ATs) and 14 extender substrates. Our ∼200 in vitro reactions resulted in 13 structurally different polyketides, including several polyketides that have not been reported. In some cases, AT-exchanged PKSs produced target polyketides by >100-fold compared to the wild-type PKS. These data also indicate that most unusual AT domains do not incorporate malonyl-CoA and methylmalonyl-CoA but incorporate various rare extender substrates that are equal to in size or slightly larger than natural substrates. We developed a computational workflow to predict the approximate AT substrate range based on active site volumes to support the selection of ATs. These results greatly enhance our understanding of rare AT domains and demonstrate the benefit of using the proposed PKS engineering strategy to produce novel chemicals in vitro.

Disulfide bond reduction and exchange in C4 domain of von Willebrand factor undermines platelet binding

BackgroundThe von Willebrand factor (VWF) is a key player in regulating hemostasis through adhesion of platelets to sites of vascular injury. It is a large, multi-domain, mechano-sensitive protein that is stabilized by a net of disulfide bridges. Binding to platelet integrin is achieved by the VWF-C4 domain, which exhibits a fixed fold, even under conditions of severe mechanical stress, but only if critical internal disulfide bonds are closed. ObjectiveTo determine the oxidation state of disulfide bridges in the C4 domain of VWF and implications for VWF’s platelet binding function. MethodsWe combined classical molecular dynamics and quantum mechanical simulations, mass spectrometry, site-directed mutagenesis, and platelet binding assays. ResultsWe show that 2 disulfide bonds in the VWF-C4 domain, namely the 2 major force-bearing ones, are partially reduced in human blood. Reduction leads to pronounced conformational changes within C4 that considerably affect the accessibility of the integrin-binding motif, and thereby impair integrin-mediated platelet binding. We also reveal that reduced species in the C4 domain undergo specific thiol/disulfide exchanges with the remaining disulfide bridges, in a process in which mechanical force may increase the proximity of specific reactant cysteines, further trapping C4 in a state of low integrin-binding propensity. We identify a multitude of redox states in all 6 VWF-C domains, suggesting disulfide bond reduction and swapping to be a general theme. ConclusionsOur data suggests a mechanism in which disulfide bonds dynamically swap cysteine partners and control the interaction of VWF with integrin and potentially other partners, thereby critically influencing its hemostatic function.

Effects of dynamic changes of desiccation cracks on preferential flow: experimental investigation and numerical modeling

Abstract. Preferential flow induced by desiccation cracks (PF-DC) has been proven to be an important hydrological effect that could cause various geotechnical engineering and ecological environment problems. Investigation on the PF-DC remains a great challenge due to the soil shrinking–swelling behavior. This work presents an experimental and numerical study of the PF-DC considering the dynamic changes of desiccation cracks. A soil column test was conducted under wetting–drying cycles to investigate the dynamic changes of desiccation cracks and their hydrological response. The ratios between the crack area and soil matrix area (crack ratio), crack aperture and depth were measured. The soil water content, matrix suction and water drainage were monitored. A new dynamic dual-permeability preferential flow model (DPMDy) was developed, which includes physically consistent functions in describing the variation of both porosity and hydraulic conductivity in crack and matrix domains. Its performance was compared to the single-domain model (SDM) and rigid dual-permeability model (DPM) with fixed crack ratio and hydraulic conductivity. The experimental results showed that the maximum crack ratio and aperture decreased when the evaporation intensity was excessively raised. The self-closure phenomenon of cracks and increased surficial water content was observed during low-evaporation periods. The simulation results showed that the matrix evaporation modeled by the DPMDy is lower than that of the SDM and DPM, but its crack evaporation is the highest. Compared to the DPM, the DPMDy simulated a faster pressure head building-up process in the crack domain and higher water exchange rates from the crack to the matrix domain during rainfall. Using a fixed crack ratio in the DPM, whether it is the maximum or the average value from the experiment data, will overestimate the infiltration fluxes of PF-DC but underestimate its contribution to the matrix domain. In conclusion, the DPMDy better described the underlying physics involving crack evolution and hydrological response with respect to the SDM and DPM. Further improvement of the DPMDy should focus on the hysteresis effect of the soil water retention curve and soil deformation during wetting–drying cycles.

Acyltransferase Domain Exchange between Two Independent Type I Polyketide Synthases in the Same Producer Strain of Macrolide Antibiotics.

Streptomyces graminofaciens A-8890 produces two macrolide antibiotics, FD-891 and virustomycin A, both of which show significant biological activity. In this study, we identified the virustomycin A biosynthetic gene cluster, which encodes type I polyketide synthases (PKSs), ethylmalonyl-CoA biosynthetic enzymes, methoxymalony-acyl carrier protein biosynthetic enzymes, and post-PKS modification enzymes. Next, we demonstrated that the acyltransferase domain can be exchanged between the Vsm PKSs and the PKSs involved in FD-891 biosynthesis (Gfs PKSs), without any supply problems of the unique extender units. We exchanged the malonyltransferase domain in the loading module of Gfs PKS with the ethylmalonyltransferase domain and the methoxymalonyltransferase domain of Vsm PKSs. Consequently, the expected two-carbon-elongated analog 26-ethyl-FD-891 was successfully produced with a titer comparable to FD-891 production by the wild type; however, exchange with the methoxymalonyltransferase domain did not produce any FD-891 analogs. Furthermore, 26-ethyl-FD-891 showed potent cytotoxic activity against HeLa cells, like natural FD-891.

Ethosuximide is an allosteric blocker of girk channels with Gβγ and is subunit dependent.

Ethosuximide (ETX) is a common drug in the treatment of absence epilepsy. ETX is known to act via inhibition of T-type voltage gated Ca2+ channels. Later, it was shown that ETX blocks GIRK channels as well. Recently, ETX was shown to reduce absence-like epileptiform activity in mice carrying disease-causing mutations in GNB1 gene, which encodes for Gβ1 subunit. Gβγ subunits are the main gating factor of GIRK channels. Here, we study the mechanism by which ETX blocks GIRK channels. We confirmed that CaV3.2, as well as CaV1.2 channels are weakly blocked by ETX at therapeutic doses (0.25-0.75 mM), as was shown previously. Homotetrameric GIRK2 channels co-expressed with Gβγ subunits were almost completely inhibited at therapeutic doses of ETX, while heterotetrameric GIRK1/2 channels were mildly inhibited, and GIRK1/3 were non-sensitive. We found that the open channel mutant GIRK2N94H or ivermectin activated GIRK2WT channel were not sensitive to ETX, suggesting that it is not an open channel blocker. The affinity of ETX to GIRK2 homotetramers was increased with increasing doses of Gβγ, suggesting an allosteric inhibition. Exchange of the GIRK2 transmembrane domain (TM) with GIRK3's (GIRK2G3TM) turned the channel non-sensitive to ETX block, the opposite exchange made GIRK3G2TM more sensitive to ETX block. This data suggests that ETX blocks GIRK channels in subunit-dependent manner, it is an allosteric- rather than open channel blocker, and its binding site may be located within the TM or extracellular domain of the channel.

Charting the Lipopeptidome of Nonpathogenic Pseudomonas.

A major source of pseudomonad-specialized metabolites is the nonribosomal peptide synthetases (NRPSs) assembling siderophores and lipopeptides. Cyclic lipopeptides (CLPs) of the Mycin and Peptin families are frequently associated with, but not restricted to, phytopathogenic species. We conducted an in silico analysis of the NRPSs encoded by lipopeptide biosynthetic gene clusters in nonpathogenic Pseudomonas genomes, covering 13 chemically diversified families. This global assessment of lipopeptide production capacity revealed it to be confined to the Pseudomonas fluorescens lineage, with most strains synthesizing a single type of CLP. Whereas certain lipopeptide families are specific for a taxonomic subgroup, others are found in distant groups. NRPS activation domain-guided peptide predictions enabled reliable family assignments, including identification of novel members. Focusing on the two most abundant lipopeptide families (Viscosin and Amphisin), a portion of their uncharted diversity was mapped, including characterization of two novel Amphisin family members (nepenthesin and oakridgin). Using NMR fingerprint matching, known Viscosin-family lipopeptides were identified in 15 (type) species spread across different taxonomic groups. A bifurcate genomic organization predominates among Viscosin-family producers and typifies Xantholysin-, Entolysin-, and Poaeamide-family producers but most families feature a single NRPS gene cluster embedded between cognate regulator and transporter genes. The strong correlation observed between NRPS system phylogeny and rpoD-based taxonomic affiliation indicates that much of the structural diversity is linked to speciation, providing few indications of horizontal gene transfer. The grouping of most NRPS systems in four superfamilies based on activation domain homology suggests extensive module dynamics driven by domain deletions, duplications, and exchanges. IMPORTANCE Pseudomonas species are prominent producers of lipopeptides that support proliferation in a multitude of environments and foster varied lifestyles. By genome mining of biosynthetic gene clusters (BGCs) with lipopeptide-specific organization, we mapped the global Pseudomonas lipopeptidome and linked its staggering diversity to taxonomy of the producers, belonging to different groups within the major Pseudomonas fluorescens lineage. Activation domain phylogeny of newly mined lipopeptide synthetases combined with previously characterized enzymes enabled assignment of predicted BGC products to specific lipopeptide families. In addition, novel peptide sequences were detected, showing the value of substrate specificity analysis for prioritization of BGCs for further characterization. NMR fingerprint matching proved an excellent tool to unequivocally identify multiple lipopeptides bioinformatically assigned to the Viscosin family, by far the most abundant one in Pseudomonas and with stereochemistry of all its current members elucidated. In-depth analysis of activation domains provided insight into mechanisms driving lipopeptide structural diversification.

Micelle‐crosslinked hydrogels with stretchable, self‐healing, and selectively adhesive properties: Random copolymers work as dynamic yet self‐sorting domains

AbstractThe design of crosslinking domains is a vital factor to create functional hydrogels with controlled physical, mechanical, and adhesive properties. This paper demonstrates versatile synthetic systems of micelle‐crosslinked hydrogels with highly stretchable, self‐healing, and selectively adhesive properties. For this, methacrylate‐bearing random copolymer micelles are designed as physical and covalent crosslink domains via the self‐assembly of amphiphilic random copolymers carrying hydrophilic poly(ethylene glycol) (PEG), hydrophobic butyl or dodecyl groups, and methacrylate‐terminal PEG in water. The size, aggregation number, and pendant methacrylate number of the micelles are controlled by the composition and degree of polymerization. Hydrogels are efficiently obtained from the free radical polymerization of hydrophilic monomers such as PEG acrylate and acrylamide in the presence of the micelle crosslinkers in water. Owing to the dynamic yet selective chain exchange properties of the micelle domains, the hydrogels are highly stretchable up to over 1000% and show self‐healing and selectively adhesive properties. The self‐healing of hydrogels is promoted upon heating due to the fast chain exchange of the micelle domains, whereas hydrogels consisting of micelles with different alkyl groups are never adhesive because of their self‐sorting properties.