Phenological trends in the pre- and post-breeding migration of long-distance migratory birds.

Phenological mismatch is often cited as a putative driver of population declines in long-distance migratory birds. The mechanisms and cues utilized to advance breeding ground arrival will impact the adaptability of species to further warming. Furthermore, timing of post-breeding migration potentially faces diverging selective pressures, with earlier onset of tropical dry seasons favouring migration advancement, while longer growing seasons in temperate areas could facilitate delayed departures. Despite this, few studies exist of migration phenology on the non-breeding grounds or on post-breeding passage. Here, we use first arrival and last departure dates of 20 species of trans-Saharan migratory birds from tropical non-breeding grounds (The Gambia), between 1964 and 2019. Additionally, we use first arrival and last departure dates, as well as median arrival and departure dates, at an entry/departure site to/from Europe (Gibraltar), between 1991 and 2018. We assess phenological trends in pre- and post-breeding migration, as well as individual species' durations of stay in breeding and non-breeding areas. Furthermore, we assess the extent to which inter-annual variation in these timings may be explained by meteorological and ecological variables. We find significant advances in pre-breeding migration at both locations, while post-breeding migration is delayed. At Gibraltar, these trends do not differ between first/last and median dates of migration. The combination of these trends suggests substantial changes in the temporal usage of the two continents by migratory birds. Duration of stay (of species, not individuals) within Europe increased by 16 days, on average, over the 27-year monitoring period. By contrast, duration of species' stays on the non-breeding range declined by 63 days, on average, over the 56-year monitoring period. Taken together these changes suggest substantial, previously unreported alterations to annual routines in Afro-Palaearctic migrants.

Injectable biomimetic liquid crystalline scaffolds enhance muscle stem cell transplantation.

Muscle stem cells are a potent cell population dedicated to efficacious skeletal muscle regeneration, but their therapeutic utility is currently limited by mode of delivery. We developed a cell delivery strategy based on a supramolecular liquid crystal formed by peptide amphiphiles (PAs) that encapsulates cells and growth factors within a muscle-like unidirectionally ordered environment of nanofibers. The stiffness of the PA scaffolds, dependent on amino acid sequence, was found to determine the macroscopic degree of cell alignment templated by the nanofibers in vitro. Furthermore, these PA scaffolds support myogenic progenitor cell survival and proliferation and they can be optimized to induce cell differentiation and maturation. We engineered an in vivo delivery system to assemble scaffolds by injection of a PA solution that enabled coalignment of scaffold nanofibers with endogenous myofibers. These scaffolds locally retained growth factors, displayed degradation rates matching the time course of muscle tissue regeneration, and markedly enhanced the engraftment of muscle stem cells in injured and noninjured muscles in mice.

Nucleation and Growth of Ordered Arrays of Silver Nanoparticles on Peptide Nanofibers: Hybrid Nanostructures with Antimicrobial Properties.

Silver nanoparticles have been of great interest as plasmonic substrates for sensing and imaging, catalysts, or antimicrobial systems. Their physical properties are strongly dependent on parameters that remain challenging to control such as size, chemical composition, and spatial distribution. We report here on supramolecular assemblies of a novel peptide amphiphile containing aldehyde functionality in order to reduce silver ions and subsequently nucleate silver metal nanoparticles in water. This system spontaneously generates monodisperse silver particles at fairly regular distances along the length of the filamentous organic assemblies. The metal-organic hybrid structures exhibited antimicrobial activity and significantly less toxicity toward eukaryotic cells. Metallized organic nanofibers of the type described here offer the possibility to create hydrogels, which integrate the useful functions of silver nanoparticles with controllable metallic content.

Hierarchical assembly of collagen peptide triple helices into curved disks and metal ion-promoted hollow spheres.

A 27 amino acid collagen-based peptide (Hbyp3) was designed to radially display nine hydrophobic bipyridine moieties from a triple helical scaffold. Self-assembly of such functionalized triple helices led to the formation of micrometer-scaled disks with a curved morphology, presumably mediated by aromatic interactions, with a height that is in the range of the length of the triple helical peptide. Higher order assembly of these curved disks into micrometer-sized hollow spheres was accomplished through metal-ligand interactions between bipyridine groups of the disks and metal ions such as Fe(II), Co(II), Zn(II) and Cu(II). The thickness of the shell of these hollow spheres corresponds well with the thickness of the collagen peptide-based triple helix and the corresponding self-assembled disks. Addition of a metal ion chelator was found to reverse the assembly of the hollow spheres back to the curved disk structures. These data support the formation of the hollow spheres from the self-assembled disks of Hbyp3 upon addition of metal ions.

Metal-mediated tandem coassembly of collagen peptides into banded microstructures.

The ability to recapitulate the features of natural collagen at the micro- and nanoscale with novel biopolymers has the potential to lead to improved biomaterials. Herein we describe stimuli-responsive collagen-based peptides (IdaCol and HisCol) that together form higher order assemblies in the presence of added metal ions. SEM and TEM imaging of these assemblies revealed microscale petal-like and intertwined fiber morphologies, each with periodic banding on the nanometer scale. The observed banding is consistent with tandem coassembly of alternating IdaCol and HisCol triple helical blocks that may laterally associate either in or out of register to form higher order structures, and mimics the banding found in natural collagen fibers.

Birds with multiple homes. The annual cycle of the pallid swift (Apus pallidus brehmorum).

We tracked pallid swifts (Apus pallidus brehmorum) from a single breeding colony in Gibraltar over two years. Our results show movement of birds between specific regions within the non-breeding geographical area at specific times of the year. The tracking of a single individual showed remarkable fidelity to the areas visited between years. Furthermore, two pallid swifts tracked over the entire eight-month non-breeding period, while in Africa, gave no indication of coming to land, supporting previous findings of an airborne existence in swifts outside the breeding season. In addition, the crossing of the Sahara Desert to and from breeding grounds is remarkably fast, with one individual crossing it in just over a day. We discuss our findings in the context of bird migration evolutionary strategies.

Crag Martin neontology complements taphonomy at the Gorham's Cave Complex.

Species present in the fossil record may continue to exist at an archaeological site, allowing study that fine-tunes our picture of the ecological past. A large wintering population of Eurasian Crag Martins Ptyonoprogne rupestris (ECM) roosts at the 'Gorham's Cave Complex' UNESCO World Heritage site in Gibraltar, which is best known for its occupation by Neanderthals at times when ECMs were also present. Its complex geomorphology allows the study of use of different micro-sites (caves) within the roost. We used mark-recapture to test whether birds showed fidelity to micro-sites for roosting, and for differences in condition of birds across micro-sites. ECM showed very high fidelity towards micro-sites, within and between years, with > 90% chance of recapture at caves where they were first caught. Condition of birds differed between micro-sites, suggesting differences in roost quality between caves; birds were more likely to be recaptured at the micro-site where birds were in best condition, indicating higher survivorship. Our results demonstrate extremely fine-scale fidelity at the largest roosting site documented for ECM globally. Implications for conservation are discussed. The study provides current knowledge of a bird that has been using these caves since the Pleistocene and more generally on these caves as refuges.

Inhibitors of anthrax lethal factor based upon N-oleoyldopamine.

The structural features of an anthrax lethal factor inhibitor, N-oleoyldopamine (OLDA, 1) have been probed. The oleic acid moiety is critical, but, more interestingly, the presence of the double bond and its geometry were found to play an essential role. One compound, 5, was found to be an uncompetitive inhibitor of lethal factor (LF) with a K(i) value of 2.2microM and a cell-based IC(50) value of 4.3microM.

Peptide Amphiphile Nanostructures for Targeting of Atherosclerotic Plaque and Drug Delivery.

Co-assembled peptide amphiphile nanofibers designed to target atherosclerotic plaque and enhance cholesterol efflux are shown to encapsulate and deliver a liver X receptor agonist to increase efflux from murine macrophages in vitro. Fluorescence microscopy reveals that the nanofibers, which display an apolipoprotein-mimetic peptide, localize at plaque sites in LDL receptor knockout mice with or without the encapsulated molecule, while nanofibers displaying a scrambled, non-targeting peptide sequence do not demonstrate comparable binding. These results show that nanofibers functionalized with apolipoprotein-mimetic peptides may be effective vehicles for intravascular targeted drug delivery to treat atherosclerosis.

Mimicking the Bioactivity of Fibroblast Growth Factor-2 Using Supramolecular Nanoribbons.

Fibroblast growth factor (FGF-2) is a multifunctional growth factor that has pleiotropic effects in different tissues and organs. In particular, FGF-2 has a special role in angiogenesis, an important process in development, wound healing, cell survival, and differentiation. Therefore, incorporating biological agents like FGF-2 within therapeutic biomaterials is a potential strategy to create angiogenic bioactivity for the repair of damaged tissue caused by trauma or complications that arise from age and/or disease. However, the use of growth factors as therapeutic agents can be costly and does not always bring about efficient tissue repair due to rapid clearance from the targeted site. An alternative would be a stable supramolecular nanostructure with the capacity to activate the FGF-2 receptor that can also assemble into a scaffold deliverable to tissue. We report here on peptide amphiphiles that incorporate a peptide known to activate the FGF-2 receptor and peptide domains that drive its self-assembly into supramolecular nanoribbons. These FGF2-PA nanoribbons displayed the ability to increase the proliferation and migration of the human umbilical vein endothelial cells (HUVECs) in vitro to the same extent as the native FGF-2 protein at certain concentrations. We confirmed that this activity was specific to the FGFR1 signaling pathway by tracking the phosphorylation of downstream signaling effectors such ERK1/2 and pH3. These results indicated the specificity of FGF2-PA nanoribbons in activating the FGF-2 signaling pathway and its potential application as a supramolecular scaffold that can be used in vivo as an alternative to the encapsulation and delivery of the native FGF-2 protein.

Tissue-Factor Targeted Peptide Amphiphile Nanofibers as an Injectable Therapy To Control Hemorrhage.

Noncompressible torso hemorrhage is a leading cause of mortality in civilian and battlefield trauma. We sought to develop an i.v.-injectable, tissue factor (TF)-targeted nanotherapy to stop hemorrhage. Tissue factor was chosen as a target because it is only exposed to the intravascular space upon vessel disruption. Peptide amphiphile (PA) monomers that self-assemble into nanofibers were chosen as the delivery vehicle. Three TF-binding sequences were identified (EGR, RLM, and RTL), covalently incorporated into the PA backbone, and shown to self-assemble into nanofibers by cryo-transmission electron microscopy. Both the RLM and RTL peptides bound recombinant TF in vitro. All three TF-targeted nanofibers bound to the site of punch biopsy-induced liver hemorrhage in vivo, but only RTL nanofibers reduced blood loss versus sham (53% reduction, p < 0.05). Increasing the targeting ligand density of RTL nanofibers yielded qualitatively better binding to the site of injury and greater reductions in blood loss in vivo (p < 0.05). In fact, 100% RTL nanofiber reduced overall blood loss by 60% versus sham (p < 0.05). Evaluation of the biocompatibility of the RTL nanofiber revealed that it did not induce RBC hemolysis, did not induce neutrophil or macrophage inflammation at the site of liver injury, and 70% remained intact in plasma after 30 min. In summary, these studies demonstrate successful binding of peptides to TF in vitro and successful homing of a TF-targeted PA nanofiber to the site of hemorrhage with an associated decrease in blood loss in vivo. Thus, this therapeutic may potentially treat noncompressible hemorrhage.

Biometry and phenology of two sibling Phylloscopus warblers on their circum-Mediterranean migrations.

The Mediterranean Sea is known as an ecological barrier for numerous migratory birds flying from European breeding grounds to African wintering sites. Birds generally avoid migration over open sea and fly over land. In the Mediterranean Basin, few land bridges or bottlenecks for migratory birds exist. The narrowest are at the western and eastern extremes: the Strait of Gibraltar and Israel. Comparative studies between these locations are extremely rare to date. Therefore, in order to elucidate the differences between the two flyways, we compared data collected simultaneously for two sister leaf warbler species, the Bonelli's Warbler complex, Phylloscopus bonelli and Phylloscopus orientalis, at ringing stations in the western Mediterranean Basin Gibraltar, and the eastern Eilat, Israel. Data on biometrics and passage dates of individuals trapped at Gibraltar and Eilat were used, and it was found that mean arrival date of Western Bonelli's Warblers at Gibraltar was 15 days later than Eastern Bonelli's Warblers at Eilat. Furthermore, Western Bonelli's Warblers had shorter wings than Eastern Bonelli's Warblers. On the other hand, birds in Eilat were in poorer body condition than individuals in Gibraltar. The comparison between geographically distant stop-over sites contributes to furthering our understanding of the development of migration strategies across ecological barriers in sibling species. Our study showed that populations that breed in southwestern Europe migrate through Gibraltar and winter in West Africa are able to accomplish migration in comparatively good body condition. This is in contrast to those that winter in East Africa, migrate through Israel and have to endure the combined challenge of crossing the Sahel, Sahara and Sinai deserts before reaching their breeding grounds across southeast Europe and southwest Asia. Hence, the discrepancies described between the western and the eastern flyway suggest that individuals in the west, in general, migrate shorter distances, have a physiologically less demanding crossing of the North African deserts and appear to stage before their crossing the Strait of Gibraltar, a privilege unavailable to the migrants of the eastern flyway.

The powerful functions of peptide-based bioactive matrices for regenerative medicine.

In an effort to develop bioactive matrices for regenerative medicine, peptides have been used widely to promote interactions with cells and elicit desired behaviors in vivo. This paper describes strategies that utilize peptide-based molecules as building blocks to create supramolecular nanostructures that emulate not only the architecture but also the chemistry of the extracellular matrix in mammalian biology. After initiating a desired regenerative response in vivo, the innate biodegradability of these systems allow for the natural biological processes to take over in order to promote formation of a new tissue without leaving a trace of the nonnatural components. These bioactive matrices can either bind or mimic growth factors or other protein ligands to elicit a cellular response, promote specific mechano-biological responses, and also guide the migration of cells with programmed directionality. In vivo applications discussed in this review using peptide-based matrices include the regeneration of axons after spinal cord injury, regeneration of bone, and the formation of blood vessels in ischemic muscle as a therapy in peripheral arterial disease and cardiovascular diseases.

Consideraciones clínicas en un paciente con hipertonicidad muscular de mentón. Reporte de caso / Clinical considerations in a patient with mint muscle hi-pertonicity. Caso report / Gestão de pacientes adultos com mordida aberta anterior por deglução atípica. Relato de caso

En ortodoncia es de relevante importancia crear una oclusión estéticamente agradable y funcional, además de lograr y preservar el óptimo atractivo facial; es mandatorio realizar un examen facial minucioso porque el equilibrio y la armonía de las diferentes partes de la cara está determinada por los tejidos du-ros y blandos. El objetivo del presente artículo es exponer la importancia de un diagnóstico integral al momento de la plani-ficación del tratamiento. El presente caso, relata el manejo ortodóntico con filosofía Roth de una paciente de 13 años de edad, raza latina, diagnosticada con relación esquelética clase II, proinclinación excesiva de los incisivos en ambos arcos, perfil convexo e hi-pertonicidad del mentón. El plan de tratamiento se planificó para corregir la y la clase II esquelética mediante extracciones de los 4 primeros premolares. Como resultado se eliminó la hipertonicidad muscular, obteniendo una competencia labial adecuada y se mejoró el perfil facial en un tiempo de 18 meses. El mane-jo de este caso resulta exitoso gracias a un diagnóstico correcto y la planifi-ca-ción del caso, permite demostrar que no solo son objetivos ortodónticos las es-tructuras óseas y dentales, sino también aquellos que ayudan a mejorar el per-fil facial del paciente. Fue necesario evaluar la relación de los labios y la barbi-lla ya que estos pueden alterarse con el tratamiento de ortodoncia.

In orthodontics It's of relevant importance to create an aesthetically pleasing and functional occlusion, in addi-tion to achieving and preserving the optimal facial attractiveness; It is mandatory to perform a thorough facial exam because the balance and harmony of the different parts of the face is determined by soft and soft tissues. The objective of this article is to expose the importance of a comprehensive diagnosis at the time of treatment planning. The present case relates the orthodontic management with Roth philosophy of a 13-year-old Latina patient, diagnosed with a class II skeletal relationship, excessive incision of the incisors in both arches, convex profile and chin-hypertonicity. The treatment plan was planned to correct the skeletal class II by extractions of the first 4 premolars. As a result, muscular hypertonicity was eliminated, obtaining adequate lip competence and the facial profile was improved in a period of 18 months. The management of this case is successful thanks to a correct diagnosis and the planning of the case, allows to demonstrate that not only are the bone and dental structures orthodontic objectives, but also those that help improve the patient's facial profile. It was necessary to evaluate the relationship of the lips and chin since these can be altered with orthodontic treatment.

A mordida aberta anterior é uma má oclusão na qual um ou mais dentes não atingem o plano oclusal e não é feito contato com seus antagonistas. Seu tratamento é difícil e há controvérsia na necessidade de uma abord-agem cirúrgica. O presente caso refere-se ao tratamento de uma paciente de 61 anos de idade, atendida na clínica do Instituto Mexicano de Ortodontia, que veio pela "separação dos seus dentes". A avaliação clínica e radiográfica apresentou classe esquelética biprotrusiva I, com sobremordida de -30% com sorriso baixo e não consoante, deglutição atípica como fator etiológico que permitiu o diagnóstico de mordida aberta anterior. O tratamento consistiu na colocação de suportes de prescrição Roth .022 com tubos até os terceiros molares superiores e inferiores, colocando os suportes mais voltados para a gengiva em relação ao centro da coroa anatômica de ambos os arcos para obter extrusão e fechamento da mordida e arco aberto de sorriso; nas centrais a 1,5 mm, laterais a 1 mm e caninos a 0,5 mm. O uso de topes oclusais posteriores e também de elásticos anteriores curtos e leves desde o primeiro dia de tratamento foi essencial. A correção da posição dos dentes foi realizada em um período de 18 meses, o que também induziu uma alteração no padrão da deglutição. Através do plano de tratamento proposto, demonstrou-se que a estabilidade da oclusão pode ser dada e que nem todo paciente com mordida aberta é candidato ao tratamento cirúrgico para correção dessa má oclusão.

Tuning the thermosensitive properties of hybrid collagen peptide-polymer hydrogels.

A hybrid hydrogel based on collagen-mimetic peptides has been designed with tunable thermosensitive properties. By changing the number of POG repeats within the collagen peptide sequence, the thermal stability of the triple helical physical crosslinks of a peptide-polymer conjugate can be altered, thus tuning the stiffness of the hydrogel as a function of temperature. This report focuses on three different thermally responsive collagen peptide, PEG-based hydrogels and validates their use as stimuli-responsive materials.

Small molecule inhibitors of anthrax toxin-induced cytotoxicity targeted against protective antigen.

Two molecular scaffolds were designed using the CAVEAT molecular design package to inhibit the oligomerization of protective antigen (PA(63) ), a key protein component of anthrax toxin. The inhibitors were designed to prevent heptamerization of PA(63) by mimicking key residues of PA(63) needed for the intermolecular interactions that stabilize the heptamer. Using the scaffolds identified by CAVEAT, seven candidate inhibitors were synthesized and tested for their ability to inhibit anthrax toxin-induced cytotoxicity, with three of the agents demonstrating modest inhibition in murine J774A.1 macrophage cells.

A collagen peptide-based physical hydrogel for cell encapsulation.

Collagen peptide-based hydrogels are prepared and characterized for application in 3D cell growth. Physical hydrogels are formed by covalently linking a collagen-based peptide to an 8-arm poly(ethylene glycol) star polymer. The resulting viscoelastic hydrogels have the ability to melt into a liquid-like state near the melting temperature of the collagen triple helix and reform back into an elastic-state at room temperature, adding a thermoresponsive feature to the material. In addition, the hydrogels possess desirable stiffness, as well as a highly cross-linked network of pores where cells are found to reside, making the hydrogels promising scaffolds for the culture of hMSCs.