Equivocal support for the climate variability hypothesis within a Neotropical bird assemblage.

The climate variability hypothesis posits that an organism's exposure to temperature variability determines the breadth of its thermal tolerance and has become an important framework for understanding variation in species' susceptibilities to climate change. For example, ectotherms from more thermally stable environments tend to have narrower thermal tolerances and greater sensitivity to projected climate warming. Among endotherms, however, the relationship between climate variability and thermal physiology is less clear, particularly with regard to microclimate variation-small-scale differences within or between habitats. To address this gap, we explored associations between two sources of temperature variation (habitat type and vertical forest stratum) and (1) thermal physiological traits and (2) temperature sensitivity metrics within a diverse assemblage of Neotropical birds (n = 89 species). We used long-term temperature data to establish that daily temperature regimes in open habitats and forest canopy were both hotter and more variable than those in the forest interior and forest understory, respectively. Despite these differences in temperature regime, however, we found little evidence that species' thermal physiological traits or temperature sensitivity varied in association with either habitat type or vertical stratum. Our findings provide two novel and important insights. First, and in contrast to the supporting empirical evidence from ectotherms, the thermal physiology of birds at our study site appears to be largely decoupled from local temperature variation, providing equivocal support for the climate variability hypothesis in endotherms. Second, we found no evidence that the thermal physiology of understory forest birds differed from that of canopy or open-habitat species-an oft-invoked, yet previously untested, mechanism for why these species are so vulnerable to environmental change.

Antimicrobial-loaded biodegradable nanoemulsions for efficient clearance of intracellular pathogens in bacterial peritonitis.

Intracellular pathogenic bacteria use immune cells as hosts for bacterial replication and reinfection, leading to challenging systemic infections including peritonitis. The spread of multidrug-resistant (MDR) bacteria and the added barrier presented by host cell internalization limit the efficacy of standard antibiotic therapies for treating intracellular infections. We present a non-antibiotic strategy to treat intracellular infections. Antimicrobial phytochemicals were stabilized and delivered by polymer-stabilized biodegradable nanoemulsions (BNEs). BNEs were fabricated using different phytochemicals, with eugenol-loaded BNEs (E-BNEs) affording the best combination of antimicrobial efficacy, macrophage accumulation, and biocompatibility. The positively-charged polymer groups of the E-BNEs bind to the cell surface of macrophages, facilitating the entry of eugenol that then kills the intracellular bacteria without harming the host cells. Confocal imaging and flow cytometry confirmed that this entry occurred mainly via cholesterol-dependent membrane fusion. As eugenol co-localized and interacted with intracellular bacteria, antibacterial efficacy was maintained. E-BNEs reversed the immunosuppressive effects of MRSA on macrophages. Notably, E-BNEs did not elicit resistance selection after multiple exposures of MRSA to sub-therapeutic doses. The E-BNEs were highly effective against a murine model of MRSA-induced peritonitis with better bacterial clearance (99 % bacteria reduction) compared to clinically-employed treatment with vancomycin. Overall, these findings demonstrate the potential of E-BNEs in treating peritonitis and other refractory intracellular infections.

A global meta-analysis of the impacts of forest fragmentation on biotic mutualisms and antagonisms.

Forest fragmentation is a grave threat to biodiversity. Forests are becoming increasingly fragmented with more than 70% now < 1 km from forest edge. Although much is known about the effects of forest fragmentation on individual species, much less is understood about its effects on species interactions (i.e., mutualisms, antagonisms, etc.). In 2014, a previous meta-analysis assessed the impacts of forest fragmentation on different species interactions, across 82 studies. We pooled the previous data with data published in the last 10 years (combined total 104 studies and 168 effect sizes). We compared the new set of publications (22 studies and 32 effect sizes) with the old set to evaluate potential changes in species interactions over time given the global increase in fragmentation rates. Mutualisms were more negatively affected by forest fragmentation than antagonisms (p < 0.0001). Edge effects, fragment size, and degradation negatively affected mutualisms, but not antagonisms, a different finding from the original meta-analysis. Parasitic interactions increased as fragment size decreased (p < 0.0001)-an intriguing result at variance with earlier studies. New publications showed a more negative mean effect size of forest fragmentation on mutualisms than old publications. Although research is still limited for some interactions, we identified an important scientific trend: current research tends to focus on antagonisms. We concluded that forest fragmentation disrupts important species interactions and that this disruption has increased over time.

Metaanálisis Mundial del Impacto de la Fragmentación de Bosques sobre el Mutualismo y Antagonismo Biótico Resumen La fragmentación del bosque es una amenaza grave para la biodiversidad. Los bosques están más fragmentados, pues más del 70% tienen < 1 km a partir del borde del bosque. Aunque hay mucha información del efecto de la fragmentación sobre las especies, hay poco conocimiento de sus efectos sobre las interacciones entre especies (mutualismo, antagonismo, etc.). Un metaanálisis realizado en 2014 por evaluó en 82 estudios el impacto de la fragmentación del bosque sobre las diferentes interacciones entre especies. Juntamos estos datos con datos publicados en los últimos diez años (total combinado de 104 estudios y 168 tamaños de efecto). Comparamos el grupo nuevo de publicaciones (22 estudios y 32 tamaños de efecto) con el grupo de para evaluar los cambios potenciales en las interacciones entre especies con el tiempo dado el incremento mundial de la tasa de fragmentación. El mutualismo fue más afectado negativamente por la fragmentación del bosque que los antagonismos (p < 0.0001). El efecto del borde, tamaño del fragmento y la degradación tuvieron un efecto negativo sobre el mutualismo, pero no sobre el antagonismo, un resultado diferente al del metaanálisis original. Las interacciones parasitarias incrementaron conforme se redujo el tamaño del fragmento (p < 0.0001)-un resultado intrigante en discrepancia con los primeros resultados. Las publicaciones recientes mostraron un tamaño promedio de efecto de la fragmentación del bosque más negativo para el mutualismo que las publicaciones antiguas. Aunque hay poca investigación sobre algunas interacciones, identificamos una tendencia científica importante: la investigación actual tiende a enfocarse en los antagonismos. Concluimos que la fragmentación del bosque altera las interacciones importantes entre especies y que este cambio ha aumentado con el tiempo.

Non-viral vaccination through cationic guanidium polymer-pDNA polyplex mediated gene transfer.

Vaccination through cellular transfection of nucleotide-based vaccines is a powerful approach to combatting disease. Plasmid DNA (pDNA) vaccines are particularly promising vectors for non-viral immunomodulation that afford high degrees of potency and flexibility. Versatile guanidinium-functionalized poly(oxanorbornene)imide (PONI-Guan) homopolymers were used to facilitate non-disruptive pDNA condensation into discrete polyplexes, enabling efficient in vitro transfection of endothelial cells and HD-11 macrophages. Translation of these vectors for vaccination of white leghorn chickens against Newcastle disease virus (NDV) elicited strong humoral immune responses against the virus. This approach presents a highly versatile method for targeted immunomodulation in vivo, with the potential for translatability as a non-viral vaccine platform.

Harmonizing spatial scales and ecological theories to predict avian richness and functional diversity within forest ecosystems.

Classic ecological theory has proven that temperature, precipitation and productivity organize ecosystems at broad scales and are generalized drivers of biodiversity within different biomes. At local scales, the strength of these predictors is not consistent across different biomes. To better translate these theories to localized scales, it is essential to determine the links between drivers of biodiversity. Here we harmonize existing ecological theories to increase the predictive power for species richness and functional diversity. We test the relative importance of three-dimensional habitat structure as a link between local and broad-scale patterns of avian richness and functional diversity. Our results indicate that habitat structure is more important than precipitation, temperature and elevation gradients for predicting avian species richness and functional diversity across different forest ecosystems in North America. We conclude that forest structure, influenced by climatic drivers, is essential for predicting the response of biodiversity with future shifts in climatic regimes.

Engineered Polymer-siRNA Polyplexes Provide Effective Treatment of Lung Inflammation.

Uncontrolled inflammation is responsible for acute and chronic diseases in the lung. Regulating expression of pro-inflammatory genes in pulmonary tissue using small interfering RNA (siRNA) is a promising approach to combatting respiratory diseases. However, siRNA therapeutics are generally hindered at the cellular level by endosomal entrapment of delivered cargo and at the organismal level by inefficient localization in pulmonary tissue. Here we report efficient anti-inflammatory activity in vitro and in vivo using polyplexes of siRNA and an engineered cationic polymer (PONI-Guan). PONI-Guan/siRNA polyplexes efficiently deliver siRNA cargo to the cytosol for highly efficient gene knockdown. Significantly, these polyplexes exhibit inherent targeting to inflamed lung tissue following intravenous administration in vivo. This strategy achieved effective (>70%) knockdown of gene expression in vitro and efficient (>80%) silencing of TNF-α expression in lipopolysaccharide (LPS)-challenged mice using a low (0.28 mg/kg) siRNA dosage.

Effects of forest fragmentation on avian breeding activity.

Biodiversity declines and ecosystem decay follow forest fragmentation; initially, abundant species may become rare or be extirpated. Underlying mechanisms behind delayed extirpation of certain species following forest fragmentation are unknown. Species declines may be attributed to an inadequate number of breeding adults required to replace the population or decreased juvenile survival rate due to reduced recruitment or increased nest predation pressures. We used 10 years of avian banding data, 5 years before and 4 years after fragment isolation, from the Biological Dynamics of Forest Fragments Project, carried out near Manaus, Brazil, to investigate the breeding activity hypothesis that there is less breeding activity and fewer young after relative to before fragment isolation. We compared the capture rates of active breeding and young birds in 3 forest types (primary forest, fragment before isolation, and fragment after isolation) and the proportion of active breeding and young birds with all birds in each unique fragment type before and after isolation. We grouped all bird species by diet (insectivore or frugivore) and nesting strategy (open cup, cavity, or enclosed) to allow further comparisons among forest types. We found support for the breeding activity hypothesis in insectivorous and frugivorous birds (effect sizes 0.45 and 0.53, respectively) and in birds with open-cup and enclosed nesting strategies (effect sizes 0.56 and 0.44, respectively) such that on average there were more breeding birds in fragments before isolation relative to after isolation. A larger proportion of birds in the community were actively breeding before fragment isolation (72%) than after fragment isolation (11%). Unexpectedly, there was no significant decrease in the number of young birds after fragment isolation, although sample sizes for young were small (n = 43). This may have been due to sustained immigration of young birds to fragments after isolation. Together, our results provide some of the strongest evidence to date that avian breeding activity decreases in response to fragment isolation, which could be a fundamental mechanism contributing to ecosystem decay.

Efectos de la fragmentación del bosque sobre la actividad reproductiva de las aves Resumen Les declinaciones de la biodiversidad y el deterioro de los ecosistemas van después de la fragmentación forestal; al inicio, las especies abundantes pueden volverse raras o ser extirpadas. Todavía no se conocen los mecanismos subyacentes detrás de la extirpación retrasada de ciertas especies después de la fragmentación forestal. La declinación de las especies puede atribuirse a un número inadecuado de adultos reproductivos requeridos para reemplazar a la población o a la tasa reducida de supervivencia de los juveniles debido al reclutamiento disminuido o al incremento en la presión de depredación de los nidos. Usamos diez años de datos de anillamiento de aves, cinco años antes y cuatro años después del aislamiento por fragmentación, tomados del Proyecto Dinámica Biológica de Fragmentos de Bosque realizado cerca de Manaos, Brasil, para investigar la hipótesis de actividad reproductiva que sostiene que hay una menor actividad reproductiva y menos crías después del aislamiento por fragmentación que antes del aislamiento. Comparamos las tasas de captura de aves con reproducción activa y aves juveniles en tres tipos de bosque (primario, fragmento antes del aislamiento y fragmento después del aislamiento) y la proporción de las aves juveniles y con reproducción activa con todas las aves en cada tipo de fragmento único antes y después del aislamiento. Agrupamos todas las especies de aves según su dieta (insectívora o frugívora) y su estrategia de anidación (nido abierto, cavidad o nido cerrado) para poder realizar más comparaciones entre los tipos de bosque. Las aves con dieta insectívora y frugívora (tamaño del efecto: 0.45 y 0.53, respectivamente) y aquellas con nidos abiertos y cerrados (tamaño del efecto: 0.56 y 0.44, respectivamente) respaldaron la hipótesis de la actividad reproductora de tal manera que en promedio hubo más aves reproductoras en los fragmentos antes del aislamiento que después del aislamiento. Una gran parte de las aves de la comunidad tuvieron reproducción activa antes del aislamiento por fragmentación (72%) que después del aislamiento (11%). Sorprendentemente, no hubo una disminución significativa en el número de aves juveniles después del aislamiento, si bien el tamaño de la muestra de este grupo fue reducido (n = 43). Lo anterior pudo deberse a la continua inmigración de juveniles a los fragmentos después del aislamiento. En conjunto, nuestros resultados proporcionan algunos de los indicios más claros de que la actividad reproductiva de las aves disminuye como respuesta al aislamiento por fragmentación, lo cual podría ser un mecanismo fundamental del deterioro de los ecosistemas.

Direct discrimination of cell surface glycosylation signatures using a single pH-responsive boronic acid-functionalized polymer.

Cell surface glycans serve fundamental roles in many biological processes, including cell-cell interaction, pathogen infection, and cancer metastasis. Cancer cell surface have alternative glycosylation to healthy cells, making these changes useful hallmarks of cancer. However, the diversity of glycan structures makes glycosylation profiling very challenging, with glycan 'fingerprints' providing an important tool for assessing cell state. In this work, we utilized the pH-responsive differential binding of boronic acid (BA) moieties with cell surface glycans to generate a high-content six-channel BA-based sensor array that uses a single polymer to distinguish mammalian cell types. This sensing platform provided efficient discrimination of cancer cells and readily discriminated between Chinese hamster ovary (CHO) glycomutants, providing evidence that discrimination is glycan-driven. The BA-functionalized polymer sensor array is readily scalable, providing access to new diagnostic and therapeutic strategies for cell surface glycosylation-associated diseases.

All-natural gelatin-based bioorthogonal catalysts for efficient eradication of bacterial biofilms.

Bioorthogonal catalysis mediated by transition metal catalysts (TMCs) presents a versatile tool for in situ generation of diagnostic and therapeutic agents. The use of 'naked' TMCs in complex media faces numerous obstacles arising from catalyst deactivation and poor water solubility. The integration of TMCs into engineered inorganic scaffolds provides 'nanozymes' with enhanced water solubility and stability, offering potential applications in biomedicine. However, the clinical translation of nanozymes remains challenging due to their side effects including the genotoxicity of heavy metal catalysts and unwanted tissue accumulation of the non-biodegradable nanomaterials used as scaffolds. We report here the creation of an all-natural catalytic "polyzyme", comprised of gelatin-eugenol nanoemulsion engineered to encapsulate catalytically active hemin, a non-toxic iron porphyrin. These polyzymes penetrate biofilms and eradicate mature bacterial biofilms through bioorthogonal activation of a pro-antibiotic, providing a highly biocompatible platform for antimicrobial therapeutics.

Macrophage-Encapsulated Bioorthogonal Nanozymes for Targeting Cancer Cells.

Macrophages migrate to tumor sites by following chemoattractant gradients secreted by tumor cells, providing a truly active targeting strategy for cancer therapy. However, macrophage-based delivery faces challenges of cargo loading, control of release, and effects of the payload on the macrophage vehicle. We present a strategy that employs bioorthogonal "nanozymes" featuring transition metal catalysts (TMCs) to provide intracellular "factories" for the conversion of prodyes and prodrugs into imaging agents and chemotherapeutics. These nanozymes solubilize and stabilize the TMCs by embedding them into self-assembled monolayer coating gold nanoparticles. Nanozymes delivered into macrophages were intracellularly localized and retained activity even after prolonged (72 h) incubation. Significantly, nanozyme-loaded macrophages maintained their inherent migratory ability toward tumor cell chemoattractants, efficiently killing cancer cells in cocultures. This work establishes the potential of nanozyme-loaded macrophages for tumor site activation of prodrugs, providing readily tunable dosages and delivery rates while minimizing off-target toxicity of chemotherapeutics.

Long-term changes in avian biomass and functional diversity within disturbed and undisturbed Amazonian rainforest.

Recent long-term studies in protected areas have revealed the loss of biodiversity, yet the ramifications for ecosystem health and resilience remain unknown. Here, we investigate how the loss of understory birds, in the lowest stratum of the forest, affects avian biomass and functional diversity in the Amazon rainforest. Across approximately 30 years in the Biological Dynamics of Forest Fragments Project, we used a historical baseline of avian communities to contrast the avian communities in today's primary forest with those in modern disturbed habitat. We found that in primary rainforest, the reduced abundance of insectivorous species led to reduced functional diversity, but no reduction of biomass, indicating that species with similar functional traits are less likely to coexist in modern primary forests. Because today's forests contain fewer functionally redundant species-those with similar traits-we argue that avian communities in modern primary Amazonian rainforests are less resilient, which may ultimately disrupt the ecosystem in dynamic and unforeseen ways.

Degradable ZnS-Supported Bioorthogonal Nanozymes with Enhanced Catalytic Activity for Intracellular Activation of Therapeutics.

Bioorthogonal catalysis using transition-metal catalysts (TMCs) provides a toolkit for the in situ generation of imaging and therapeutic agents in biological environments. Integrating TMCs with nanomaterials mimics key properties of natural enzymes, providing bioorthogonal "nanozymes". ZnS nanoparticles provide a platform for bioorthogonal nanozymes using ruthenium catalysts embedded in self-assembled monolayers on the particle surface. These nanozymes uncage allylated profluorophores and prodrugs. The ZnS core combines the non-toxicity and degradability with the enhancement of Ru catalysis through the release of thiolate surface ligands that accelerate the rate-determining step in the Ru-mediated deallylation catalytic cycle. The maximum rate of reaction (Vmax) increases ∼2.5-fold as compared to the non-degradable gold nanoparticle analogue. The therapeutic potential of these bioorthogonal nanozymes is demonstrated by activating a chemotherapy drug from an inactive prodrug with efficient killing of cancer cells.

Maintenance of local adaptation despite gene flow in a coastal songbird.

Adaptation to local environments is common in widespread species and the basis of ecological speciation. The song sparrow (Melospiza melodia) is a widespread, polytypic passerine that occurs in shrubland habitats throughout North America. We examined the population structure of two parapatric subspecies that inhabit different environments: the Atlantic song sparrow (M. m. atlantica), a coastal specialist, and the eastern song sparrow (M. m. melodia), a shrubland generalist. These populations lacked clear mitochondrial population structure, yet coastal birds formed a distinct nuclear genetic cluster. We found weak overall genomic differentiation between these subspecies, suggesting either recent divergence, extensive gene flow, or a combination thereof. There was a steep genetic cline at the transition to coastal habitats, consistent with isolation by environment, not isolation by distance. A phenotype under divergent selection, bill size, varied with the amount of coastal ancestry in transitional areas, but larger bill size was maintained in coastal habitats regardless of ancestry, further supporting a role for selection in the maintenance of these subspecies. Demographic modeling suggested a divergence history of limited gene flow followed by secondary contact, which has emerged as a common theme in adaptive divergence across taxa.

Cytosolic Protein Delivery Using Modular Biotin-Streptavidin Assembly of Nanocomposites.

Current strategies for the delivery of proteins into cells face general challenges of endosomal entrapment and concomitant degradation of protein cargo. Efficient delivery directly to the cytosol overcomes this obstacle: we report here the use of biotin-streptavidin tethering to provide a modular approach to the generation of nanovectors capable of a cytosolic delivery of biotinylated proteins. This strategy uses streptavidin to organize biotinylated protein and biotinylated oligo(glutamate) peptide into modular complexes that are then electrostatically self-assembled with a cationic guanidinium-functionalized polymer. The resulting polymer-protein nanocomposites demonstrate efficient cytosolic delivery of six biotinylated protein cargos of varying size, charge, and quaternary structure. Retention of protein function was established through efficient cell killing via delivery of the chemotherapeutic enzyme granzyme A. This platform represents a versatile and modular approach to intracellular delivery through the noncovalent tethering of multiple components into a single delivery vector.

Direct Cytosolic Delivery of Proteins Using Lyophilized and Reconstituted Polymer-Protein Assemblies.

PURPOSE: Cytosolic delivery of proteins accesses intracellular targets for chemotherapy and immunomodulation. Current delivery systems utilize inefficient endosomal pathways of uptake and escape that lead to degradation of delivered cargo. Cationic poly(oxanorbornene)imide (PONI) polymers enable highly efficient cytosolic delivery of co-engineered proteins, but aggregation and denaturation in solution limits shelf life. In the present study we evaluate polymer-protein nanocomposite vehicles as candidates for lyophilization and point-of-care resuspension to provide a transferrable technology for cytosolic protein delivery. METHODS: Self-assembled nanocomposites of engineered poly(glutamate)-tagged (E-tagged) proteins and guanidinium-functionalized PONI homopolymers were generated, lyophilized, and stored for 2 weeks. After reconstitution and delivery, cytosolic access of E-tagged GFP cargo (GFPE15) was assessed through diffuse cytosolic and nuclear fluorescence, and cell killing with chemotherapeutic enzyme Granzyme A (GrAE10). Efficiency was quantified between freshly prepared and lyophilized samples. RESULTS: Reconstituted nanocomposites retained key structural features of freshly prepared assemblies, with minimal loss of material. Cytosolic delivery (> 80% efficiency of freshly prepared nanocomposites) of GFPE15 was validated in several cell lines, with intracellular access validated and quantified through diffusion into the nucleus. Delivery of GrAE10 elicited significant tumorigenic cell death. Intracellular access of cytotoxic protein was validated through cell viability. CONCLUSION: Reconstituted nanocomposites achieved efficient cytosolic delivery of protein cargo and demonstrated therapeutic applicability with delivery of GrAE10. Overall, this strategy represents a versatile and highly translatable method for cytosolic delivery of proteins.

High affinity protein surface binding through co-engineering of nanoparticles and proteins.

Control over supramolecular recognition between proteins and nanoparticles (NPs) is of fundamental importance in therapeutic applications and sensor development. Most NP-protein binding approaches use 'tags' such as biotin or His-tags to provide high affinity; protein surface recognition provides a versatile alternative strategy. Generating high affinity NP-protein interactions is challenging however, due to dielectric screening at physiological ionic strengths. We report here the co-engineering of nanoparticles and protein to provide high affinity binding. In this strategy, 'supercharged' proteins provide enhanced interfacial electrostatic interactions with complementarily charged nanoparticles, generating high affinity complexes. Significantly, the co-engineered protein-nanoparticle assemblies feature high binding affinity even at physiologically relevant ionic strength conditions. Computational studies identify both hydrophobic and electrostatic interactions as drivers for these high affinity NP-protein complexes.

Supramolecular arrangement of protein in nanoparticle structures predicts nanoparticle tropism for neutrophils in acute lung inflammation.

This study shows that the supramolecular arrangement of proteins in nanoparticle structures predicts nanoparticle accumulation in neutrophils in acute lung inflammation (ALI). We observed homing to inflamed lungs for a variety of nanoparticles with agglutinated protein (NAPs), defined by arrangement of protein in or on the nanoparticles via hydrophobic interactions, crosslinking and electrostatic interactions. Nanoparticles with symmetric protein arrangement (for example, viral capsids) had no selectivity for inflamed lungs. Flow cytometry and immunohistochemistry showed NAPs have tropism for pulmonary neutrophils. Protein-conjugated liposomes were engineered to recapitulate NAP tropism for pulmonary neutrophils. NAP uptake in neutrophils was shown to depend on complement opsonization. We demonstrate diagnostic imaging of ALI with NAPs; show NAP tropism for inflamed human donor lungs; and show that NAPs can remediate pulmonary oedema in ALI. This work demonstrates that structure-dependent tropism for neutrophils drives NAPs to inflamed lungs and shows NAPs can detect and treat ALI.

Protein-Based Films as Antifouling and Drug-Eluting Antimicrobial Coatings for Medical Implants.

Nosocomial infections, caused by bacterial contamination of medical devices and implants, are a serious healthcare concern. We demonstrate here, the use of fluorous-cured protein nanofilm coatings for generating antimicrobial surfaces. In this approach, bacteria-repelling films are created by heat-curing proteins in fluorous media. These films are then loaded with antibiotics, with release controlled via electrostatic interactions between therapeutic and protein film building blocks to provide bactericidal surfaces. This film fabrication process is additive-free, biocompatible, biodegradable, and can be used to provide antimicrobial coatings for both three-dimensional (2D) and 3D objects for use in indwelling devices.

What is Known-and not Known-About Acoustic Communication in an Urban Soundscape.

Urban environments have some of the most highly modified soundscapes on the planet, affecting the way many animals communicate using acoustic signals. Communication involves transmission of information via signals, such as bird song, between a signaler and a receiver. Much work has focused on the effects of urbanization on signalers and their signals, yet very little is known about how noise pollution affects receiver behaviors and sensory systems. Here, we synthesize key findings to date regarding avian acoustic communication in the urban environment and delineate key gaps in knowledge for future work. We leverage our own work comparing current and historical songs from urban and rural habitats for a subspecies of white-crowned sparrows (Zonotrichia leucophrys nuttalli). We use this system, along with findings from other systems, to answer three key questions in the field: (1) Is song variation consistent with temporal and spatial variation in anthropogenic noise? (2) How are birds adjusting their song to the urban environment? (3) How does song 'urbanization' affect signal function? Our synthesis illustrates that the adjustments birds make to their songs in noisy environments can improve signal detection, but potentially at the cost of signal function. Many key gaps in knowledge need to be addressed to complete our understanding of how acoustic communication systems evolve in urban areas, specifically in regard to sexual selection and female preference, as well as how receivers perceive signals in an urban environment.