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Hydrogels are soft materials of great interest in different areas such as chemistry, biology, and therapy. Gels made by the self-assembly of small molecules are known as supramolecular gels. The modulation of their properties by monomer molecular design is still difficult to predict due to the potential impact of subtle structural modifications in the self-assembly process. Herein, we introduce the design principles of a new family of self-assembling cyclic octapeptides of alternating chirality that can be used as scaffolds for the development of self-healing hydrogelator libraries with tunable properties. The strategy was used in the preparation of an amphiphilic cyclic peptide monomer bearing an alkoxyamine connector, which allowed the insertion of different aromatic aldehyde pendants to modulate the hydrophobic/hydrophilic balance and fine-tune the properties of the resulting gel. The resulting amphiphiles were able to form self-healable hydrogels with viscoelastic properties (loss tangent, storage modulus), which were strongly dependent on the nature and number of aromatic moieties anchored to the hydrophilic peptide. Structural studies by SEM, STEM and AFM indicated that the structure of the hydrogels was based on a dense network of peptide nanotubes. Excellent agreement was established between the peptide primary structure, nanotube length distributions and viscoelastic behaviour.

Modes of reproduction in animals are diverse, with different modes having evolved independently in multiple lineages across a variety of taxa. However, an understanding of the genomic change driving the transition between different modes of reproduction is limited. Several ricefishes (Adrianichthyidae) on the island of Sulawesi have a unique mode of reproduction called "pelvic-fin brooding," wherein females carry externally fertilized eggs until hatching using their pelvic fins. Phylogenomic analysis demonstrated pelvic-fin brooders to have evolved at least twice in two distant clades of the Adrianichthyidae. We investigated the genetic architecture of the evolution of this unique mode of reproduction. Morphological analyses and laboratory observations revealed that females of pelvic-fin brooders have longer pelvic fins and a deeper abdominal concavity, and that they can carry an egg clutch for longer than nonbrooding adrianichthyids, suggesting that these traits play important roles in this reproductive mode. Quantitative trait locus mapping using a cross between a pelvic-fin brooder Oryzias eversi and a nonbrooding O. dopingdopingensis reveals different traits involved in pelvic-fin brooding to be controlled by different loci on different chromosomes. Genomic analyses of admixture detected no signatures of introgression between two lineages with pelvic-fin brooders, indicating that introgression is unlikely to be responsible for repeated evolution of pelvic-fin brooding. These findings suggest that multiple independent mutations may have contributed to the convergent evolution of this novel mode of reproduction.

The membrane translocation of hydrophilic substances constitutes a challenge for their application as therapeutic compounds and labelling probes1–4. To remedy this, charged amphiphilic molecules have been classically used as carriers3,5. However, such amphiphilic carriers may cause aggregation and non-specific membrane lysis6,7. Here we show that globular dodecaborate clusters, and prominently B12Br122−, can function as anionic inorganic membrane carriers for a broad range of hydrophilic cargo molecules (with molecular mass of 146–4,500 Da). We show that cationic and neutral peptides, amino acids, neurotransmitters, vitamins, antibiotics and drugs can be carried across liposomal membranes. Mechanistic transport studies reveal that the carrier activity is related to the superchaotropic nature of these cluster anions8–12. We demonstrate that B12Br122− affects cytosolic uptake of different small bioactive molecules, including the antineoplastic monomethyl auristatin F, the proteolysis targeting chimera dBET1 and the phalloidin toxin, which has been successfully delivered in living cells for cytoskeleton labelling. We anticipate the broad and distinct delivery spectrum of our superchaotropic carriers to be the starting point of conceptually distinct cell-biological, neurobiological, physiological and pharmaceutical studies.

Self-assembling cyclic peptide nanotubes are supramolecular structures whose diameter and external surface properties are precisely controlled. In this communication we describe a general strategy to align different molecules on top of the nanotube surface by using cyclic peptides bearing chemoreversible reactive groups. D,L-α-Cyclic peptides endowed with a hydrazide moiety were condensed with a pyrenecarboxyaldehyde to facilitate the nanotube formation and deposition on flat unfunctionalized surfaces. The hydrazide moieties can be liberated without affecting the tubular structure and then used to align on top of the nanotube other molecules bearing aldehyde functions. Additionally, the attachment of specific ligands allowed the supramolecular alignment of corresponding receptors, such as mannosyl aldehyde and concavaline-A, driven by the nanotube structure through complemetary protein–ligand interactions This work was supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (PID2019 111126RB-100, SAF2017-89890-R, EIG_JC2018-054), and by the Xunta de Galicia and the ERDF (ED431C 2017/25 and Centro singular de Investigación de Galicia accreditation 2019-2022, ED431G 2019/03). We also thank the ORFEO-CINCA network and Mineco (RED2018-102331-T). J.M.P. thanks to the Ministerio de Educación y Cultura (MEC) for his FPI contract. J.M. received an ISCIII (COV20/00297), ERC - Stg (DYNAP-677786), ERC-PoC (TraffikGene, 838002),and a YIG from the HFSP (RGY0066/2017) 2022-12-20 SI

IntroductionBotrynema, a genus of medusozoans in the trachyline family Halicreatidae, currently contains two species: B. brucei and B. ellinorae, distinguished by the presence or absence, respectively, of an apical knob as a diagnostic character. However, no study has corroborated if these taxonomic diagnoses have a biological and evolutionary basis. Therefore, in this study we attempted to address the question “do the two nominal species in the genus Botrynema represent independent phylogenetic lineages, or two phenotypic variants of a single species?MethodsIn this study we took advantage of legacy collections from different research expeditions across the globe from 2000 to 2021 to study the phylogenetics and taxonomy of the genus Botrynema.ResultsB. brucei and B. ellinorae present partially overlapping vertical distributions in the Arctic and as a whole in the Arctic the genus seems to be limited to the Atlantic water masses. The phylogenetic reconstruction based on the concatenated alignment corroborates the validity of the family Halicreatidae and of genus Botrynema as monophyletic groups. However no clear differentiation was found between the two presently accepted species, B. ellinorae and B. brucei.DiscussionBased on the evidence we gathered, we conclude that while the genus Botrynema does contain at least two species lineages, these lineages are not concordant with current species definitions. The species B. ellinorae is reassigned as a subspecies of B. brucei and diagnostic characters are provided.

The self-assembly of peptides and proteins frequently shows structural plasticity depending on subtle alterations. The acquisition of structural data of these peptide assemblies with atomic level precision will be crucial to understand and predict assembled morphologies.

The two-dimensional (2D) homogeneous assembly of nanoparticle monolayer arrays onto a broad range of substrates constitutes an important challenge for chemistry, nanotechnology, and material science. α-Synuclein (αS) is an intrinsically disordered protein associated with neuronal protein complexes and has a high degree of structural plasticity and chaperone activity. The C-terminal domain of αS has been linked to the noncovalent interactions of this protein with biological targets and the activity of αS in presynaptic connections. Herein, we have systematically studied peptide fragments of the chaperone-active C-terminal sequence of αS and identified a 17-residue peptide that preserves the versatile binding nature of αS. Attachment of this short peptide to gold nanoparticles afforded colloidally stable nanoparticle suspensions that allowed the homogeneous 2D adhesion of the conjugates onto a wide variety of surfaces, including the formation of crystalline nanoparticle superlattices. The peptide sequence and the strategy reported here describe a new adhesive molecule for the controlled monolayer adhesion of metal nanoparticles and sets a stepping-stone toward the potential application of the adhesive properties of αS This work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [BIO2015-70092-R, SAF2017-89890-R], the Xunta de Galicia (ED431C 2017/25, 2016-AD031, AGAUR (2017 SGR 324), and Centro Singular de Investigación de Galicia accreditation 2016–2019, ED431G/09), the ISCIII (COV20/00297), and the European Union (European Regional Development Fund – ERDF). X.S. acknowledges funding from the ERC (CONCERT-648201). IRB Barcelona is the recipient of a Severo Ochoa Award (Government of Spain). J.M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Grant (DYNAP-677786), and a Young Investigator Grant from the HFSP (RGY0066/2017) SI

Recent genetic and genomic studies have revealed tremendous diversity in sex chromosomes across diverse taxa. Although theoretical studies predict that sex chromosome evolution can drive the evolution of sexual dimorphism, empirical studies are still limited. A taxonomic group that shows diversity in both sex chromosomes and sexual dimorphism provides excellent opportunity to investigate the link between the evolution of sex chromosomes and sexual dimorphism. The medaka fishes (family Adrianichthyidae) exhibit both rapid sex chromosome turnovers and diversification of sexually dimorphic traits. In the present study, we investigated the sex chromosomes of 13 Oryzias species from Sulawesi, Indonesia, that have diversified in sexual dichromatism. Using pooled sequencing we found sex chromosomes in 9 species that all had XY systems, with a few species being possibly modified by multiple loci. Seven species (O. woworae, O. asinua, O. wolasi, O. matanensis, O. celebensis, O. hadiatyae, and O. dopingdopingensis) share linkage group (LG) 24 as sex chromosomes; however, they differed in the length and magnitude of sequence divergence between the X and Y chromosomes. The sex chromosome of O. eversi was LG4, which has not been reported as a sex chromosome in any other medaka species. In O. sarasinorum, LG16 and LG22 are associated with sex. Although LG16 was found to be sex-linked in another medaka species previously examined, the sex-determining regions did not overlap. Frequent turnovers and the great diversity of the sex chromosomes make Sulawesian medaka species a model system for investigating the roles of sex chromosome evolution in the diversification of sexual dimorphism.

The dynamic functionalization of the nanoparticle surface with biocompatible coatings is a critical step towards the development of functional nano-sized systems. While covalent approaches have been broadly exploited in the stabilization of nanoparticle colloidal systems, these strategies hinder the dynamic nanosurface chemical reconfiguration. Supramolecular strategies based on specific host–guest interactions hold promise due to their intrinsic reversibility, self-healing capabilities and modularity. Host/guest couples have recently been implemented in nanoparticle platforms for the exchange and release of effector molecules. However, the direct exchange of biocompatible hydrophilic oligomers (e.g. peptides) for the modulation of the surface charge and chemical properties of nanoparticles still remains a challenge. Here, we show the intracellular reconfiguration of nanoparticles by a host/guest mechanism with biocompatible oligomeric competitors. The surface of gold nanoparticles was functionalized with cyclodextrin hosts and the guest exchange was studied with biocompatible mono and divalent adamantyl competitors. The systematic characterization of the size and surface potential of the host/guest nanoparticles allowed the optimization of the binding and the stabilization properties of these supramolecular systems. The in cellulo host/guest-mediated direct reconfiguration of the peptide layer at the surface of nanoparticles is achieved by controlling the valence of adamantane-equipped peptides. This work demonstrates that host/guest supramolecular systems can be exploited for the direct exchange of pendants at the surface of nanoparticles and the intracellular dynamic chemical reconfiguration of biocompatible colloidal systems This work was partially supported by the Spanish AgenciaEstatal de Investigación (AEI) [SAF2017-89890-R, CTQ2014-59646-R and CTQ2016-78423-R], the Xunta de Galicia(ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF.H. F.-C. received a predoctoral fellowship (Xunta de Galicia,ED481A-2017/047). A. M.-A. received a MCIF from the EC(GLYCONANOPEP-750248). J. M. holds a Ramón y Cajal (RYC-2013-13784), an ERC-Stg (DYNAP-677786) and a Young Investigator Grant from the HFSP (RGY0066/2017) 2023-02-07 SI

Multivalent ligand presentation is a powerful strategy for the development of specific binders and inhibitors. Peptide/[60]fullerene hybrids have now been synthesized that exploit the complete substitution of the fullerene scaffold to afford globular structures presenting twelve copies of a peptide ligand for the recognition of E-selectin. Fully substituted peptide/[60]fullerene hexakis-adducts offer an excellent opportunity for multivalent protein recognition. In contrast to monofunctionalized fullerene hybrids, peptide/[60]fullerene hexakis-adducts display multiple copies of a peptide in close spatial proximity and in the three dimensions of space. High affinity peptide binders for almost any target can be currently identified by in vitro evolution techniques, often providing synthetically simpler alternatives to natural ligands. However, despite the potential of peptide/[60]fullerene hexakis-adducts, these promising conjugates have not been reported to date. Here we present a synthetic strategy for the construction of 3D multivalent hybrids that are able to bind with high affinity the E-selectin. The here synthesized fully substituted peptide/[60]fullerene hybrids and their multivalent recognition of natural receptors constitute a proof of principle for their future application as functional biocompatible materials This work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [SAF2017-89890-R, PCI2019-103400, PID2020-117143RB-I00, PID2020-114653RB-I00 and PID2020-115120GB-I00], Xunta de Galicia (ED431C 2017/25 and Centro singular de investigación de Galicia accreditation 2019–2022, ED431G 2019/03) and the European Commission (EC) (European Regional Development Fund-ERDF). J.M. thanks the ERC-STG (DYNAP, 677786), ERC-POC (TraffikGene, 838002), Xunta de Galicia (Oportunius Program) and Human Frontier Science Programme Young Investigator Grant (RGY0066/2017) for funding. J.J.R. received a Beatriz Galindo Grant (BEAGAL18-00051) by the Spanish Ministerio de Universidades. I.G. received predoctoral fellowships (ED481A-2018/116 and FPU17/00941). J.C.-G. thanks the Comunidad de Madrid Atracción de Talento program (2018-T2/BMD-10275) SI

Background: Bocas del Toro is positioned in the Pacific arc as a maritime province, linked to the Caribbean coastline, with a territory endowed with natural resources for primary and tourist production. The cross-border dimension will be a basic component of its geostrategic position, in which agriculture represents one of the foundations of sustainable development. Objective: The analysis, interpretation, and classification of the populated areas with agricultural vocation of the Changuinola district are approached in this work. Methodology: The method of Principal Component Analysis (PCA) was applied. Through the PCA the first two components that were selected explained 74.7% of the total variation. This allowed a classification in three strata, discriminating the populated areas of greater agricultural activity in the district using hierarchical and non-hierarchical cluster analysis. Results: It was detected that the factors with the greatest impact on the characteristics of the population studied were the development of agriculture in indigenous territories, low education, occupation, and the proportion of economically inactive people; this characterization serves as the first approach to the study of sustainable land management in indigenous territories. Implications: This study prioritized and typified specific characteristics of the population such as education, unemployment, and food security, thus it is a predictor in populations in conditions of vulnerability, representing the starting point for more in-depth studies in other areas of the country and even an input for the management of public policy. Conclusion: This research represents an important part in the establishment of the baseline study on the location of agricultural production in the rural development areas of the Changuinola district, the local production technology, the technical results, and the relations of the inhabitants with the environment physical.

Cyclic peptides are a fascinating class of molecules that can be programmed to fold or self-assemble into diverse mono- and multidimensional structures with potential applications in biomedicine, nanoelectronics, or catalysis. Herein we describe on-resin procedures to carry out head-to-tail peptide cyclization based on orthogonal protected linear structures. We also present essential characterization tools for obtaining dynamic and structural information, including the visualization cyclic peptide assembly into nanotubes (AFM, TEM) as well as the use of fluorescence microscopy.

Many cnidarians have been reported in association with hermit crabs from shallow waters to the deep sea. Some of these actiniarians and zoantharians produce a carcinoecium, a chitin-like pseudo-she...

Sympatric speciation has been demonstrated in few empirical case studies, despite intense searches, because of difficulties in testing the criteria for this mode of speciation. Here, we report a possible case of sympatric speciation in ricefishes of the genus Oryzias on Sulawesi, an island of Wallacea. Three species of Oryzias are known to be endemic to Lake Poso, an ancient tectonic lake in central Sulawesi. Phylogenetic analyses using RAD-seq-derived single nucleotide polymorphisms (SNPs) revealed that these species are monophyletic. We also found that the three species are morphologically distinguishable and clearly separated by population-structure analyses based on the SNPs, suggesting that they are reproductively isolated from each other. A mitochondrial DNA chronogram suggested that their speciation events occurred after formation of the tectonic lake, and existence of a historical allopatric phase was not supported by coalescent-based demographic inference. Demographic inference also suggested introgressive hybridization from an outgroup population. However, differential admixture among the sympatric species was not supported by any statistical tests. These results all concur with criteria necessary to demonstrate sympatric speciation. Ricefishes in this Wallacean lake provide a promising new model system for the study of sympatric speciation.

We here describe the synthesis and biological evaluation of glycan shields for cell penetrating peptides. A new benzyl alkoxyamine connector was employed for the coupling of two saccharides units in the lateral side chain of individual amino acids in a peptide sequence. The oxyme bond formation with the corresponding glycan aldehydes allowed the preparation of highly glycosylated penetrating peptides with a minimal synthetic effort. Surprisingly, it was found that a four to six saccharide substitution did not decrease uptake efficiency in cells, whereas it significantly improved the toxicity profile of the penetrating peptide. In particular, glucose substitution was confirmed as an optimal glycan shield that showed an excellent in vitro uptake and intracellular localization as well as a superior in vivo biodistribution The Spanish Agencia Estatal de Investigación (AEI) [SAF2017-89890-R, PCI2019-103400, PID2020-117143RB-I00], Xunta de Galicia (ED431C 2017/25, ED431G 2019/03) and the ERDF are acknowledged. J. M. thanks the ERC-Stg (DYNAP, 677786), ISCIII (COV20/00297), ERC-POC (TraffikGene, 838002), Xunta de Galicia (Oportunius Program) and Human Frontier Science Programme Young Investigator Grant (RGY0066/2017) for funding. I. G. received predoctoral fellowships (ED481A-2018/116 and FPU17/00941) 2022-12-24 SI

Antivirals are now more important than ever. To efficiently inhibit virus replication, antiviral multivalent strategies need sufficient affinity to overcome the excellent matching between the virus and its receptor. This report highlights a phage capsid scaffold strategy that can be used to precisely position sialic acid moieties to inhibit influenza A virus replication.

In this work we report a rational design strategy for the identification of new peptide prototypes for the non-disruptive supramolecular permeation of membranes and the transport of different macromolecular giant cargos. The approach targets a maximal enhancement of helicity in the presence of membranes with sequences bearing the minimal number of cationic and hydrophobic moieties. The here reported folding enhancement in membranes allowed the selective non-lytic translocation of different macromolecular cargos including giant proteins. The transport of different high molecular weight polymers and functional proteins was demonstrated in vesicles and in cells with excellent efficiency and optimal viability. As a proof of concept, functional monoclonal antibodies were transported for the first time into different cell lines and cornea tissues by exploiting the helical control of a short peptide sequence. This work introduces a rational design strategy that can be employed to minimize the number of charges and hydrophobic residues of short peptide carriers to achieve non-destructive transient membrane permeation and transport of different macromolecules., The helical enhancement of a short oligoalanine peptide scaffold in anionic membranes triggered the supramolecular assembly of a nanopore, which allowed the transport and release of proteins in the cytosol of cells and tissues.

Sulawesi, an island located in a biogeographical transition zone between Indomalaya and Australasia, is famous for its high levels of endemism. Ricefishes (family Adrianichthyidae) are an example of taxa that have uniquely diversified on this island. It was demonstrated that habitat fragmentation due to the Pliocene juxtaposition among tectonic subdivisions of this island was the primary factor that promoted their divergence; however, it is also equally probable that habitat fusions and resultant admixtures between phylogenetically distant species may have frequently occurred. Previous studies revealed that some individuals of Oryzias sarasinorum endemic to a tectonic lake in central Sulawesi have mitochondrial haplotypes that are similar to the haplotypes of O. eversi, which is a phylogenetically related but geologically distant (ca. 190 km apart) adrianichthyid endemic to a small lake. In this study, we tested if this reflects ancient admixture of O. eversi and O. sarasinorum. Population genomic analyses of genome-wide single-nucleotide polymorphisms revealed that O. eversi and O. sarasinorum are substantially reproductively isolated from each other. Comparison of demographic models revealed that the models assuming ancient admixture from O. eversi to O. sarasinorum was more supported than the models assuming no admixture; this supported the idea that the O. eversi-like mitochondrial haplotype in O. sarasinorum was introgressed from O. eversi. This study is the first to demonstrate ancient admixture of lacustrine organisms in Sulawesi beyond 100 km. The complex geological history of this island enabled such island-wide admixture of lacustrine organisms, which usually experience limited migration.

An increasing volume of empirical studies demonstrated that hybridization between distant lineages may have promoted speciation in various taxa. However, the timing, extent and direction of introgressive hybridization remain unknown in many cases. Here, we report a possible case in which repeated hybridization promoted divergence of Oryzias ricefishes (Adrianichthyidae) on Sulawesi, an island of Wallacea. Four Oryzias species are endemic to the Malili Lake system in central Sulawesi, which is composed of five tectonic lakes; of these, one lake is inhabited by two species. Morphological and population genomic analyses of genome-wide single-nucleotide polymorphisms revealed that these two sympatric species are phylogenetically sister to but substantially reproductively isolated from each other. Analyses of admixture and comparison of demographic models revealed that the two sympatric species experienced several substantial introgressions from outgroup populations that probably occurred soon after they had secondary contact with each other in the lake. However, the ratio of migrants from the outgroups was estimated to be different between the two species, which is consistent with the hypothesis that these introgressions aided their divergence or prevented them from forming a hybrid swarm. Repeated lake fragmentations and fusions may have promoted diversification of this freshwater fish species complex that is endemic to this ancient lake system.

This is the peer reviewed version of the following article: S. Díaz, I. Insua, G. Bhak, J. Montenegro, Chem. Eur. J. 2020, 26, 14765, which has been published in final form at https://doi.org/10.1002/chem.202003265. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. The inherent ability of peptides to self-assemble with directional and rationally predictable interactions has fostered a plethora of synthetic two-dimensional (2D) supramolecular biomaterials. However, the design of peptides with hierarchical assembly in different dimensions across mesoscopic lengths remains a challenging task. We here describe the structural exploration of a d/l-alternating cyclic octapeptide capable of assembling one-dimensional (1D) nanotubes in water, which subsequently pack laterally to form giant 2D nanosheets up to 500 μm long with a constant 3.2 nm thickness. Specific amino acid mutations allowed the mapping of structure–assembly relationships that determine 2D self-assembly. Nine peptide modifications were studied, revealing key features in the peptide sequence that nanosheets tolerated, while a total of three peptide variants included modifications that compromised their 2D arrangement. These lessons will serve as guide and inspiration for new 2D supramolecular peptide designs This work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [SAF2017-89890-R], Xunta de Galicia (AD031 2016, ED431C 2017/25 and ED431G2019/03) and the European Commission (EC) (European Regional Development Fund-ERDF) Instituto de Salud Carlos III (COV20/00297). I.I. thanks the European Commission (EC) and AEI for MSCA-IF (2018-843332) and Juan de la Cierva (FJCI-2017-31795) fellowships, respectively. J.M. thanks the Ramón y Cajal (RYC-2013-13784), ERC- STG (DYNAP, 2016-677786), ERC-POC (TraffikGene, 2019-838002) and Human Frontier Science Programme Young Investigator Grant (RGY0066/2017) for funding SI

The recent advances in the supramolecular polymerization of synthetic building blocks in aqueous conditions has given rise to new artificial and biocompatible functional materials. However, despite the importance of spatially resolved self‐assembly for natural and artificial molecular machines, the spatial control of supramolecular polymerization with synthetic monomers has not been experimentally established yet. Here we describe a microfluidic‐regulated tandem process of supramolecular polymerization and droplet encapsulation to control the position of self‐assembled microfibrillar bundles of cyclic peptide nanotubes in water droplets. This method allowed the precise preferential localization of the fibres either at the interface or into the core of the droplets. UV absorbance, circular dichroism and fluorescence microscopy indicated that the microfluidic control of the stimuli (changes in pH or ionic strength) can be employed to adjust the packing degree and the spatial position of microfibrillar bundles of cyclic peptide nanotubes. Additionally, this spatially organized supramolecular polymerization of peptide nanotubes was applied in the assembly of highly ordered two‐dimensional droplet networks This work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [SAF2017-89890-R, CTQ2016-78423-R], the Xunta de Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF. A. M.-A. received a MCIF from the EC (GLYCONANOPEP-750248). J. M. holds a Ramón y Cajal (RYC-2013-13784), an ERC-Stg (DYNAP-677786) and a Young Investigator Grant from the HFSP (RGY0066/2017). J. R. G. thanks to the mobility program (PRX17/00147) SI

This is the Accepted Manuscript of the following article: Méndez-Ardoy, A., Granja, J., & Montenegro, J. (2018). pH-Triggered self-assembly and hydrogelation of cyclic peptide nanotubes confined in water micro-droplets. Nanoscale Horizons. http://dx.doi.org/10.1039/c8nh00009c The controlled one-dimensional supramolecular polymerization of synthetic building blocks in confined spaces constitutes a key challenge to simplify the understanding of the fundamental physical principles behind the behavior of more complex encapsulated polymer networks. Cyclic peptide nanotubes constitute an optimal scaffold for the fabrication of hierarchical one-dimensional self-assembled architectures. Herein we report the pH-controlled nanotube formation and fibrillation of supramolecular cyclic peptides in confined aqueous droplets. The externally triggered self-assembly of these peptides gave rise to viscoelastic hydrogels in which the one-dimensional molecular arrangement was perfectly preserved from the nano- to the micro-scale. The cyclic peptide building blocks were confined inside water microdroplets and the base-triggered supramolecular polymerization was externally triggered and followed by confocal microscopy showing that the confined fibrillation spanned and affected the shape of the droplet micro container This work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [SAF2017-89890-R, CTQ2014-59646-R and CTQ2016-78423-R], the Xunta de Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF. A. M.-A. received a MCIF from the EC (GLYCONANOPEP-750248). J. M. holds a Ramón y Cajal (RYC-2013-13784), an ERC-Stg (DYNAP-677786) and a Young Investigator Grant from the HFSP (RGY0066/2017) SI

The Indian subcontinent has an origin geologically different from Eurasia, but many terrestrial animal and plant species on it have congeneric or sister species in other parts of Asia, especially in the Southeast. This faunal and floral similarity between India and Southeast Asia is explained by either of the two biogeographic scenarios, ‘into-India’ or ‘out-of-India’. Phylogenies based on complete mitochondrial genomes and five nuclear genes were undertaken for ricefishes (Adrianichthyidae) to examine which of these two biogeographic scenarios fits better. We found that Oryzias setnai , the only adrianichthyid distributed in and endemic to the Western Ghats, a mountain range running parallel to the western coast of the Indian subcontinent, is sister to all other adrianichthyids from eastern India and Southeast–East Asia. Divergence time estimates and ancestral area reconstructions reveal that this western Indian species diverged in the late Mesozoic during the northward drift of the Indian subcontinent. These findings indicate that adrianichthyids dispersed eastward ‘out-of-India’ after the collision of the Indian subcontinent with Eurasia, and subsequently diversified in Southeast–East Asia. A review of geographic distributions of ‘out-of-India’ taxa reveals that they may have largely fuelled or modified the biodiversity of Eurasia.

Many straits in the Japanese archipelago have been proposed as biogeographical boundaries, but there is disagreement regarding their importance as historic barriers against dispersal of terrestrial and freshwater taxa. Mitochondrial DNA haplotype and phylogenetic analyses of Lefua nikkonis, a primary freshwater fish inhabiting northern Japan and descendent from Siberia, revealed that the species is genetically structured within its geographic range, but that two major haplotypes are widely distributed across the Ishikari Lowland of Hokkaido Island as well as across the Tsugaru Strait between Hokkaido and Honshu Islands, two well-known biogeographical boundaries of northern Japan. The two major haplotypes were separated from each other by only one mutational step, and many other haplotypes, including those endemic to the region south of these barriers, have diverged from the major haplotypes, suggesting rapid range expansion and local differentiation. Divergence-time estimates, based on vicariance of the Honshu endemic congener L. echigonia via uplift of the Central Highlands, demonstrated that the southward dispersal of L. nikkonis from Hokkaido Island to Honshu Island occurred less than 0.08–0.19 Mya, suggesting that a land bridge emerged at the Tsugaru Strait during the Riss glaciation. Given that other freshwater taxa crossed the strait earlier (during the Middle Pleistocene), it is likely that land bridges in the strait have repeatedly emerged. The fact that L. nikkonis invaded only the northern part of Honshu, and that many other freshwater species also have the limit of their distribution ranges in this area as well, indicates that a faunal transition zone might persist even without the Tsugaru Strait. Thus, straits and lowlands in northern Japan are likely to have been less important as dispersal barriers to freshwater taxa than is currently thought.

The Red Sea was one of the first areas of the Indo-Pacific to be investigated by marine taxonomists, and the literature on suborder Brachycnemina (Anthozoa: Hexacorallia: Zoantharia) for this region dates from the early nineteenth century. However, in the last 100 years there has been only one focused study on this group in the Red Sea. In the present study, specimens collected from the Saudi Arabian coast of the northern half of the Red Sea were phylogenetically analyzed by sequencing nuclear internal transcribed spacer regions of ribosomal DNA (ITS-rDNA), mitochondrial cytochrome oxidase subunit I (COI), and 16S ribosomal DNA (16S–rDNA). The new results were compared with historical data in the literature and recent results from the Persian Gulf and the southeastern coast of Africa. Results show the presence of six to seven potential Brachycnemina species in the Red Sea; five to six Palythoa species (Palythoa mutuki, P. tuberculosa, P. cf. heliodiscus, P. aff. heliodiscus, and one to two species within the P. sp. “sakurajimensis” group) together with Zoanthus sansibaricus. While P. mutuki, P. tuberculosa, and Z. sansibaricus are known to be widely distributed in the Indo-Pacific, P. cf. heliodiscus and P. sp. “sakurajimensis” have not been reported from the Persian Gulf or the southeastern coast of Africa, and the current results represent large range extensions for these two species. Only one of the observed species, P. aff. heliodiscus, is potentially endemic to the Red Sea, further demonstrating the generally wide distributions of most zooxanthellate Brachycnemina species.

Here we present the synthesis and post-polymerisation modification of poly(acryloyl hydrazide), a versatile scaffold for the preparation of functional polymers: poly(acryloyl hydrazide) was prepared from commercially available starting materials in a three step synthesis on a large scale, in good yields and high purity. Our synthetic approach included the synthesis of a Boc-protected acryloyl hydrazide, the preparation of polymers via RAFT polymerisation and the deprotection of the corresponding Boc-protected poly(acryloyl hydrazide). Post-polymerisation modification of poly(acryloyl hydrazide) was then demonstrated using a range of conditions for both hydrophilic and hydrophobic aldehydes. These experiments demonstrate the potential of poly(acryloyl hydrazide) as a scaffold in the synthesis of functional polymers, in particular those applications where in situ screening of the activity of the functionalised polymers may be required (e.g. biological applications) This work was supported by the Royal Society, U.K (IE130688) and the Wellcome Trust (177ISSFPP). F. F.-T. thanks the Birmingham Science City and the European Regional Development Fund, the Royal Society (RG140273), and the University of Birmingham (John Evans Fellowship). J. M. thanks funding from MINECO (CTQ2014-59646-R, RYC-2013-1378) the Xunta de Galicia (ED431G/09 and 2016-AD031) and the ERC (Stg-DYNAP-677786) SI

Tracking the pH with spatiotemporal resolution is a critical challenge for synthetic chemistry, chemical biology and beyond. Over the last decade different small probes and supramolecular systems have emerged for in celluloor in vivo pH tracking. However, pH reporting still presents critical limitations such as background reduction, sensor improved stability, cell targeting, endosomal escape, near and far infrared ratiometric pH tracking, adaptation to the new imaging techniques (i.e. super‐resolution), etc. These challenges will demand the combined efforts of synthetic and supramolecular chemistry working together to develop a next generation of smart materials that will resolve the current limitations. In this review we describe the recent advances in the synthesis of small fluorescent probes together with new supramolecular functional systems employed for pH tracking with emphasis in ratiometric probes. The combination of organic synthesis and stimuli‐responsive supramolecular functional materials will be essential to solve future challenges of pH tracking such as the improved signal to noise ratio, on target activation and microenvironment reporting This work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [SAF2017-89890-R], the Xunta de Galicia (ED431C 2017/25, 2016-AD031 and Centro Singular de Investigación de Galicia accreditation 2016–2019, ED431G/09), the ISCIII (RD16/0008/003), and the European Union (European Regional Development Fund –ERDF). A.M. received a Marie Curie fellowship (GLYCONANOPEP-750248). J.M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP-677786) and a Young Investigator Grant from the Human Frontier Science Research Program (RGY0066/2017) SI

Although there are many examples of color evolution potentially driven by sensory drive, only few studies have examined whether distinct species inhabiting the same environments evolve similar body colors via shared sensory mechanisms. In this study, we tested whether two sympatric freshwater fish taxa, halfbeaks of the genus Nomorhamphus and ricefishes of the genus Oryzias in Sulawesi Island, converge in both body color and visual sensitivity. After reconstructing the phylogeny separately for Nomorhamphus and Oryzias using transcriptome‐wide sequences, we demonstrated positive correlations of body redness between these two taxa across environments, even after phylogenetic corrections, which support convergent evolution. However, substantial differences were observed in the expression profiles of opsin genes in the eyes between Nomorhamphus and Oryzias. Particularly, the expression levels of the long wavelength‐sensitive genes were negatively correlated between the taxa, indicating that they have different visual sensitivities despite living in similar light environments. Thus, the convergence of body colorations between these two freshwater fish taxa was not accompanied by convergence in opsin sensitivities. This system presents a case in which body color convergence can occur between sympatric species via different mechanisms.

The formation of oligomeric soluble aggregates is related to the toxicity of amyloid peptides and proteins. In this manuscript, we report the use of a ruthenium polypyridyl complex ([Ru(bpy)2(dpqp)]2+) to track the formation of amyloid oligomers at different times using photoluminescence anisotropy. This technique is sensitive to the rotational correlation time of the molecule under study, which is consequently related to the size of the molecule. [Ru(bpy)2(dpqp)]2+ presents anisotropy values of zero when free in solution (due to its rapid rotation and long lifetime) but larger values as the size and concentration of amyloid-β (Aβ) oligomers increase. Our assays show that Aβ forms oligomers immediately after the assay is started, reaching a steady state at ∼48 h. SDS–PAGE, DLS, and TEM were used to confirm and characterize the formation of oligomers. Our experiments show that the rate of formation for Aβ oligomers is temperature dependent, with faster rates as the temperature of the assay is increased. The probe was also effective in monitoring the formation of α-synuclein oligomers at different times AAM thanks the Welch Foundation (Grant C-1743) and JM thanks AEI (SAF2017-89890-R), ERC (DYNAP-677786) and HFSP (RGY0066/2017) for financial support SI

Ecuador subsidizes fuels, the problem with this benefit is that, many citizens are dedicated to illegally market these resources in border cities, among these fuels there are the cylinders of liquefied petroleum gas; the existing fragile control greatly benefits smuggling, representing a loss of resources for Ecuador. There is no subsidy in neighboring countries such as Peru and Colombia, and unfortunately some citizens have chosen to engage in illegal fuel marketing, generating economic losses for the country. The actual cost of a 15 kilo gas cylinder is 12.00 dollars, however, it is sold at 1.60 dollar. It means that the government subsidizes 89% of the price of gas, with barely 11% being paid by consumers. (Diario el Comercio, 2013) People who take advantage of the poor control of illegal marketing, reduce the number of cylinders in border areas of Ecuador and therefore increase the price, this situation has generated inconveniences for Ecuadorian citizens when they can not acquire gas cylinders. Currently, given the advance of technology in particular of microelectronics, it is very common to use portable electronic devices such as RFID (Radio Frequency Identifier) tags, for this project the active labels of 2.4 GHz allow the unique identification of each gas cylinder, as well as the portability of the information and the relation of belonging between gas cylinders and citizens, facilitating their monitoring and control.

Linear peptide amphiphiles are excellent biocompatible scaffolds for the hierarchical self-assembly of one dimensional nanostructures in aqueous media. However, their structural exploration and screening of self-assembling properties is often limited by time-consuming synthesis and purification steps. We here describe the application of the oxime bond as a powerful synthetic tool towards the conjugation of peptide heads bearing a hydroxylamine group with hydrophobic aldehyde tails. This methodology allowed the quick prepraration of a small library of oxime-connected peptide amphiphiles, whose supramolecular screening revealed nano-to-micro fibrillation with dependency on their chemical structure. These results demonstrate the simplicity and the synthetic potential of the oxime conjugation for the preparation of peptide amphiphiles with improved self-assembling capabilities This work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [CTQ2014-59646-R, SAF2017-89890-R], the Xunta de Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF. I.I. thanks the Spanish AEI for a Juan de la Cierva -Formación fellowship (FJCI-2017-31795). J.M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP-677786) and a Young Investigator Grant from the Human Frontier Science Research Program (RGY0066/2017) SI

The internalisation and delivery of active substances into cells is a field of growing interest for chemical biology and therapeutics. As we move from small-molecule-based drugs towards bigger cargos, such as antibodies, enzymes, nucleases or nucleic acids, the development of efficient delivery systems becomes critical for their practical application. Different strategies and synthetic carriers have been developed; these include cationic lipids, gold nanoparticles, polymers, cell-penetrating peptides (CPPs), protein surface modification etc. However, all of these methodologies still present limitations relating to the precise targeting of the different intracellular compartments and, in particular, difficulties in access to the cellular cytosol. Additionally, the precise quantification of the cellular uptake of a compound is not enough to demonstrate delivery and/or functional activity. Therefore, methods to determine cellular distributions of cargos and carriers are of critical importance for identifying the barriers that are blocking the activity. Herein we survey the different techniques that can currently be used to track and to monitor the subcellular localisation of the synthetic compounds that we deliver inside cells.

The recent advances in genetic engineering demand the development of conceptually new methods to prepare and identify efficient vectors for the intracellular delivery of different nucleotide payloads ranging from short single-stranded oligonucleotides to larger plasmid double-stranded circular DNAs. Although many challenges still have to be overcome, polymers hold great potential for intracellular nucleotide delivery and gene therapy. We here develop and apply the postpolymerization modification of polyhydrazide scaffolds, with different degree of polymerization, for the preparation of amphiphilic polymeric vehicles for the intracellular delivery of a circular plasmid DNA. The hydrazone formation reactions with a mixture of cationic and hydrophobic aldehydes proceed in physiologically compatible aqueous conditions, and the resulting amphiphilic polyhydrazones are directly combined with the biological cargo without any purification step. This methodology allowed the preparation of stable polyplexes with a suitable size and zeta potential to achieve an efficient encapsulation and intracellular delivery of the DNA cargo. Simple formulations that performed with efficiencies and cell viabilities comparable to the current gold standard were identified. Furthermore, the internalization mechanism was studied via internalization experiments in the presence of endocytic inhibitors and fluorescence microscopy. The results reported here confirmed that the polyhydrazone functionalization is a suitable strategy for the screening and identification of customized polymeric vehicles for the delivery of different nucleotide cargos This work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [CTQ2014-59646-R, CTQ2016-78423-R, SAF2017-89890-R], the Xunta de Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031), the ERDF, Royal Society U.K (IE130688 and RG140273), and the Wellcome Trust (177ISSFPP). J.M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP-677786), and a Young Investigator Grant from the Human Frontier Science Research Program (RGY0066/2017). F. F.-T. thanks the Birmingham Science City and the European Regional Development Fund, and the University of Birmingham (John Evans Fellowship). J.M.P. thanks the Spanish Agencia Estatal de Investigación (AEI) for his research contract SI

This manuscript has been accepted after peer review and appears as anAccepted Article online prior to editing, proofing, and formal publicationof the final Version of Record (VoR). This work is currently citable byusing the Digital Object Identifier (DOI) given below. The VoR will bepublished online in Early View as soon as possible and may be differentto this Accepted Article as a result of editing. Readers should obtainthe VoR from the journal website shown below when it is publishedto ensure accuracy of information. The authors are responsible for thecontent of this Accepted Article The intracellular transport of exogenous proteins has emerged as one of the most promising methodologies for biotechnology and chemical biology. Current protein delivery is mainly approached by liposome encapsulation, translational fusion and ionic/hydrophobic non‐covalent aggregation with transporting molecular vehicles. We here introduce the concept of supramolecular recognition and selective transport of proteins by peptide hybrid materials. We have designed a helical amphiphilic cationic peptide that bears two orthogonal alkoxyamines for the precise anchoring of protein ligands. After the attachment of these protein ligands, the peptide showed a high binding affinity for its protein target (i.e. mannose/Concanavalin A, Biotin/Streptavidin). The resulting peptide/protein hybrids were taken up by human cells such as HeLa and HepG2. The concept described in this manuscript could potentially be adapted, through the appropriate choice of ligands, to the transport of other proteins with suitable supramolecular binding motifs This work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [CTQ2014-59646-R, CTQ2013-43264-R, SAF2017-89890-R], the Xunta de Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF. We thank Pili Canoa (CACTI, UVIGO) for assistance with the SPR measurements. M.J. received a F.P.I. fellowship from MINECO (CTQ2014-59646-R). J.M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP- 677786) and a Young Investigator Grant from the Human Frontier Science Research Program (RGY0066/2017) SI

Binding constants, Log K ≈ 6.6 M-1, and NMR characterization of the complexes formed by sulfobetaines and cucurbit[7]uril (CB7) support the electrostatic interaction as major driving force. This very strong binding motif is cross-linked by additional CB7 molecules resulting in the formation of supramolecular nanoparticles (SNPs) with an average diameter of 172 nm and negative surface potential. The time course evolution of the particle size and the surface potential suggests the very fast formation of an amorphous aggregate that absorbs additional amount of sulfobetaine. These aggregates afford very stable (more than two weeks) nanoparticles in aqueous dispersion. The reversibility of the sulfobetaine/CB7 host:guest complexes allows SNPs disaggregation by adding a competitive guest as shown by treatment with tetraethylammonium chloride. The addition of this competitive cation triggers a SNPs to micelle transition. The potential application of these nanoparticles as drug delivery vehicles was investigated by using carboxyfluorescein. These experiments revealed that upon externally induced disruption of the SNPs (by tetraethylammonium chloride) the fluorescent dye was trapped into micellar aggregates that can be further disrupted by cyclodextrin additionhttp://www.usc.es/ Financial support from Ministerio de Economia y Competitividad of Spain (projects CTQ2014-55208-P, CTQ2017-84354-P, CTQ2014-59646-R and MAT2015-67458-P), Xunta de Galicia (GR 2007/085; IN607C 2016/03 and Centro singular de investigación de Galicia accreditation 2016-2019, ED431G/09) and the European Union (European Regional Development Fund – ERDF), is gratefully acknowledged. J.M. received a Ramón y Cajal (RYC-2013- 13784) and a starting grant from the ERC (DYNAP677786) SI

The genus Bergia was established by Duchassaing de Fonbressin and Michelotti in 1860, for two species, Bergia catelunaris and B. vialactea. Subsequently, in 1903 Duerden recognized these two species as conspecific, and used B. catelunaris in favour of B. vialactea, and transferred B. catelunaris to the genus Parazoanthus. However, over the last decade, it has been found that the genus Parazoanthus is actually polyphyletic and therefore it has gradually been divided and redefined. Based on phylogenetic analyses, Parazoanthus sensu stricto was recently limited to species which form associations with sponges, but it still comprised of three distinctive and monophyletic subclades. Of these clades, one Parazoanthus clade contains the type species for Parazoanthus, P. axinellae, while another clade was recently described as the genus Umimayanthus based on mitochondrial 16S-rDNA sequences. However, the other remaining Parazoanthus clade contains P. catenularis, the original type species of the genus Bergia. Base...

Subnanometric noble metal clusters, composed by only a few atoms, behave like molecular entities and display magnetic, luminescent and catalytic activities. However, non-covalent interactions of molecular metal clusters, lacking of any ligand or surfactant, have not been seen at work. Theoretically attractive and experimentally discernable, van der Waals forces and non-covalent interactions at the metal/organic interfaces will be crucial to understand and develop the next generation of hybrid nanomaterials. Here, we present experimental and theoretical evidence of non-covalent interactions between subnanometric metal (0) silver clusters and aromatic rings and their application in the preparation of 1D self-assembled hybrid architectures with ditopic peptide nanotubes. Atomic force microscopy, fluorescence experiments, circular dichroism and computational simulations verified the occurrence of these interactions in the clean and mild formation of a novel peptide nanotube and metal cluster hybrid materials. The findings reported here confirmed the sensitivity of silver metal clusters of small atomicity towards non-covalent interactions, a concept that could find multiple applications in nanotechnology. We conclude that induced supramolecular forces are optimal candidates for the precise spatial positioning and properties modulation of molecular metal clusters. The reported results herein outline and generalize the possibilities that non-covalent interactions will have in this emerging field This work was supported by the Spanish Ministry of Economy and Competitivity (Mineco) and the ERDF [CTQ2010-15725, CTQ2013-43264-R, MAT2011-28673-C02-01, MAT2012-36754-C02-01], by the Xunta de Galicia (GRC2006/132, GRC2013/044, EM 2012/117). J.M. received a Ramón y Cajal contract from the Mineco. We also thank the ORFEO-CINCA network and Mineco through CTQ2014-51912-REDC SI

Currently the genera Parazoanthus (family Parazoanthidae) and Epizoanthus (family Epizoanthidae) are the only sponge-associated zoantharians (Cnidaria, Anthozoa). The Parazoanthidae-sponge associations are widely distributed in tropical and subtropical waters from the intertidal to the deep sea in the Atlantic and Indo-Pacific Oceans. However, the taxonomic identification of both parties is often confused due to variable morphology and wide ecological ranges. In particular, Parazoanthidae species diversity remains poorly understood in the Indo-Pacific. In the present study, the diversity of the sponge-zoanthid association in the Indo-Pacific was investigated with 71 Parazoanthidae specimens collected from 29 different locations in Japan (n = 22), Australia (n = 6) and Florida, USA (n = 1). For all specimens morphological analyses were performed and total DNA was extracted and amplified for four DNA markers (COI-mtDNA, mt 16S-rDNA, ITS-rDNA and ALG11-nuDNA). The combined data demonstrate that the specimens of this study are clearly different from those of all described Parazoanthus species, and lead us to erect Umimayanthus gen. n., within family Parazoanthidae, containing the three newly described species U. chanpuru sp. n., U. miyabi sp. n., U. nakama sp. n. The new genus also includes the previously described species U. parasiticus (Duchassaing and Michelotti, 1860; comb. nov.), previously belonging to the genus Parazoanthus. Neighbor joining, maximum likelihood and Bayesian posterior probability phylogenetic trees clearly demonstrate the monophyly of Umimayanthus gen. n. to the exclusion of all outgroup sequences. The phylogenetic results were also compared to morphological features, and polyp sizes, amount of sand content in tissues, types of connections between polyps, and cnidae data, in particular holotrichs-1, were useful in distinguishing the different species within this new genus. This new genus can be distinguished from all other Zoantharia by a unique and conserved 9 bp insertion and a 14 bp deletion in the mt 16S-rDNA region. Additionally, compared to Parazoanthus sensu stricto (i.e. P. axinellae [Schmidt, 1862]), Umimayanthus spp. are only found associated to sponges, and have a coenenchyme much less developed than Parazoanthus sensu stricto. Each new species can be distinguished from other congeners by a unique DNA sequence, numbers of tentacle, maximum sizes of holotrichs, associated sponge morphology, and colony morphology. The identification of the host sponge species is the next logical step in this research as this may also aid in the distinction of Umimayanthus species.

The objective of this Feature Article is to reflect on the importance of established and emerging principles of supramolecular organic chemistry to address one of the most persistent problems in life sciences. The main topic is dynamic covalent chemistry on cell surfaces, particularly disulfide exchange for thiol-mediated uptake. Examples of boronate and hydrazone exchange are added for contrast, comparison and completion. Of equal importance are the discussions of proximity effects in polyions and counterion hopping, and more recent highlights on ring tension and ion pair-π interactions. These lessons from supramolecular organic chemistry apply to cell-penetrating peptides, particularly the origin of "arginine magic" and the "pyrenebutyrate trick," and the currently emerging complementary "disulfide magic" with cell-penetrating poly(disulfide)s. They further extend to the voltage gating of neuronal potassium channels, gene transfection, and the delivery of siRNA. The collected examples illustrate that the input from conceptually innovative chemistry is essential to address the true challenges in biology beyond incremental progress and random screening.

The hydrazone modulation of a penetrating peptide carrier is reported as a suitable and straightforward strategy for the delivery of Cas9 inside living cells., The discovery of RNA guided endonucleases has emerged as one of the most important tools for gene edition and biotechnology. The selectivity and simplicity of the CRISPR/Cas9 strategy allows the straightforward targeting and editing of particular loci in the cell genome without the requirement of protein engineering. However, the transfection of plasmids encoding the Cas9 and the guide RNA could lead to undesired permanent recombination and immunogenic responses. Therefore, the direct delivery of transient Cas9 ribonucleoprotein constitutes an advantageous strategy for gene edition and other potential therapeutic applications of the CRISPR/Cas9 system. The covalent fusion of Cas9 with penetrating peptides requires multiple incubation steps with the target cells to achieve efficient levels of gene edition. These and other recent reports suggested that covalent conjugation of the anionic Cas9 ribonucleoprotein to cationic peptides would be associated with a hindered nuclease activity due to undesired electrostatic interactions. We here report a supramolecular strategy for the direct delivery of Cas9 by an amphiphilic penetrating peptide that was prepared by a hydrazone bond formation between a cationic peptide scaffold and a hydrophobic aldehyde tail. The peptide/protein non-covalent nanoparticles performed with similar efficiency and less toxicity than one of the best methods described to date. To the best of our knowledge this report constitutes the first supramolecular strategy for the direct delivery of Cas9 using a penetrating peptide vehicle. The results reported here confirmed that peptide amphiphilic vectors can deliver Cas9 in a single incubation step, with good efficiency and low toxicity. This work will encourage the search and development of conceptually new synthetic systems for transitory endonucleases direct delivery.

Se ha creado un Laboratorio Virtual para detectar experimentalmente la frecuencia de oscilación de un oscilador amortiguado. Una vez que se introducen los datos de entrada como masa, constante elástica y amortiguación del medio, el módulo muestra las oscilaciones en la pantalla de la computadora, detecta automáticamente los desplazamientos extremos de la oscilación y aplica el algoritmo de Decremento Loga-rítmico, que conduce al exponente que caracteriza la contracción gradual de los desplazamientos. De este exponente se calcula la frecuencia de las oscilaciones amortiguadas oscilador, este resultado – tal como se espera- es igual al valor calculado teóricamente.

The Oryzias woworae species group, composed of O. asinua, O. wolasi, and O. woworae, is widely distributed in southeastern Sulawesi, an island in the Indo-Australian Archipelago. Deep-elongated body shape divergence is evident among these three species to the extent that it is used as a species-diagnostic character. These fishes inhabit a variety of habitats, ranging from upper streams to ponds, suggesting that the body shape divergence among the three species may reflect adaptation to local environments. First, our geometric morphometrics among eight local populations of this species group revealed that the three species cannot be separated by body shape and that riverine populations had more elongated bodies and longer caudal parts than lacustrine populations. Second, their phylogenetic relationships did not support the presence of three species; phylogenies using mitochondrial DNA and genomic data obtained from RNA-Seq revealed that the eight populations could not be sorted into three different clades representing three described species. Third, phylogenetic corrections of body shape variations and ancestral state reconstruction of body shapes demonstrated that body shape divergence between riverine and lacustrine populations persisted even if the phylogenies were considered and that body shape evolved rapidly irrespective of phylogeny. Sexual dimorphism in body shape was also evident, but the degree of dimorphism did not significantly differ between riverine and lacustrine populations after phylogenetic corrections, suggesting that sexual selection may not substantially contribute to geographical variations in body shape. Overall, these results indicate that the deep-elongated body shape divergence of the O. woworae species group evolved locally in response to habitat environments, such as water currents, and that a thorough taxonomic reexamination of the O. woworae species group may be necessary.

Very few studies have been conducted on the long-term effects of typhoon damage on mesophotic coral reefs. This study investigates the long-term community dynamics of damage from Typhoon 17 (Jelawat) in 2012 on the coral community of the upper mesophotic Ryugu Reef in Okinawa, Japan. A shift from foliose to bushy coral morphologies between December 2012 and August 2015 was documented, especially on the area of the reef that was previously recorded to be poor in scleractinian genera diversity and dominated by foliose corals. Comparatively, an area with higher diversity of scleractinian coral genera was observed to be less affected by typhoon damage with more stable community structure due to less change in dominant coral morphologies. Despite some changes in the composition of dominant genera, the generally high coverage of the mesophotic coral community is facilitating the recovery of Ryugu Reef after typhoon damage.

Gene transfection continues to be a major challenge in chemistry, biology and materials sciences. New methodologies and recent breakthroughs have renewed the interest in the discovery and development of new tools for efficient gene transfection. Hydrazone formation between a cationic head and hydrophobic tails has emerged as one of the most promising techniques for nucleotide delivery. In this contribution, we have exploited hydrazone formation to modulate the transfection activity of a parent linear peptide in combination with a plasmid DNA cargo. This strategy allowed the straightforward preparation, under physiologically compatible conditions, of a discrete library of amphiphilic modulated penetrating peptides. Without the requirement of any isolation or purification steps, these modulated amphiphilic peptides were combined with a plasmid DNA and screened in transfection experiments of human HeLa cells. Three of these hydrazone-conjugated peptides were identified as excellent vectors for plasmid delivery with comparable, or even higher, efficiencies and lower toxicity than the commercial reagents employed in routine transfection assays We are thankful to Dr. Irene Lostalé-Seijo for cell culture assistance and discussions. We acknowledge funding from the Spanish Government MINECO: [CTQ2014-59646-R] and [CTQ2015-74621-JIN], the Xunta de Galicia (ED431G/09), the ERDF and the CESGA. R. G.-F. received a FCT Investigator Grant from Portugal (IF/01133/2015). J.M. received a Ramon y Cajal (RYC-2013-13784) and an ERC Starting Investigator Grant (DYNAP-677786) SI

NOTICE: This is the peer reviewed version of the following article: Fuertes A, Juanes M, Granja J, Montenegro J. Supramolecular functional assemblies: dynamic membrane transporters and peptide nanotubular composites. Chem Commun. 2017;53(56):7861-7871. [doi: 10.1039/C7CC02997G]. This article may be used for non-commercial purposes in accordance with RSC Terms and Conditions for self-archiving The fabrication of functional molecular devices constitutes one of the most important current challenges for chemical sciences. The complex processes accomplished by living systems continuously demand the assistance of non-covalent interactions between molecular building blocks. Additionally, these building blocks (proteins, membranes, nucleotides) are also constituted by self-assembled structures. Therefore, supramolecular chemistry is the discipline required to understand the properties of the minimal self-assembled building blocks of living systems and to develop new functional smart materials. In the first part of this feature article, we highlight selected examples of the preparation of supramolecular membrane transporters with special emphasis in the application of dynamic covalent bonds. In the second section of the paper we review recent breakthroughs in the preparation of peptide nanotubes hybrids with functional applications. The development of these devices constitutes an exciting process from where we can learn how to understand and manipulate supramolecular functional assemblies We acknowledge funding from the Spanish Agencia Estatal de Investigación (AEI) (CTQ2014-59646-R and CTQ2016-78423-R), the Xunta de Galicia (ED431G/09 and 2016-AD031) and the ERDF. A. F. and M. J. received F. P. U. and F. P. I. fellowships from MECD and MINECO. J. M. received a Ramon y Cajal Grant (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP-677786) and a Young Investigator Grant from the Human Frontier Research Program (RGY0066/2017) SI

Two of the main types of nanotubular architectures are the single-walled carbon nanotubes (SWCNTs) and the self-assembling cyclic peptide nanotubes (SCPNs). We here report the preparation of the dual composite resulting from the ordered combination of both tubular motifs. In the resulting architecture, the SWCNTs can act as templates for the assembly of SCPNs that engage the carbon nanotubes noncovalently via pyrene "paddles", each member of the resulting hybrid stabilizing the other in aqueous solution. The particular hybrids obtained in the present study formed highly ordered oriented arrays and display complementary properties such as electrical conductivity. Furthermore, a self-sorting of the cyclic peptides toward semiconducting rather than metallic SWCNTs is also observed in the aqueous dispersions. It is envisaged that a broad range of exploitable properties may be achieved and/or controlled by varying the cyclic peptide components of similar SWCNT/SCPN hybrids.

A novel chemoselective one-pot transformation of acetals to silyl ethers is reported. Free hydroxyls, double bonds and triple bonds are unaffected in optimal reaction conditions. This practical, inexpensive protocol allows the selective replacement of acetal-forming protecting groups with silyl groups in a single step under mild conditions.