Detection of Felis catus Gammaherpesvirus 1 in Domestic Cat Saliva: Prevalence, Risk Factors, and Attempted Virus Isolation.

Felis catus gammaherpesvirus 1 (FcaGHV1) infects domestic cats worldwide, yet it has not been successfully propagated in cell culture, and little is known about how it is shed and transmitted. To investigate the salivary shedding of FcaGHV1, we quantified FcaGHV1 DNA in feline saliva by qPCR. For FcaGHV1-positive saliva, we sequenced a portion of the viral glycoprotein B (gB) gene and attempted to isolate the infectious virus by passage in several felid and non-felid cell lines. We detected FcaGHV1 DNA in 45/227 (19.8%) saliva samples with variable viral DNA loads from less than 100 to greater than 3 million copies/mL (median 4884 copies/mL). Multiple saliva samples collected from an infected cat over a two-month period were consistently positive, indicating that chronic shedding can occur for at least two months. Cat age, sex, and health status were not associated with shedding prevalence or viral DNA load in saliva. Feral status was also not associated with shedding prevalence. However, feral cats had significantly higher FcaGHV1 DNA load than non-feral cats. Sequencing of FcaGHV1 gB showed low sequence diversity and >99.5% nucleotide identity to the worldwide consensus FcaGHV1 gB sequence. We did not detect virus replication during the passage of FcaGHV1-positive saliva in cell culture, as indicated by consistently negative qPCR on cell lysate and supernatant. To our knowledge, these data show for the first time that cats in Canada are infected with FcaGHV1. The data further suggest that shedding of FcaGHV1 in saliva is common, can occur chronically over an extended period of time, and may occur at higher levels in feral compared to non-feral cats.

Automated classification of otitis media with OCT: augmenting pediatric image datasets with gold-standard animal model data.

Otitis media (OM) is an extremely common disease that affects children worldwide. Optical coherence tomography (OCT) has emerged as a noninvasive diagnostic tool for OM, which can detect the presence and quantify the properties of middle ear fluid and biofilms. Here, the use of OCT data from the chinchilla, the gold-standard OM model for the human disease, is used to supplement a human image database to produce diagnostically relevant conclusions in a machine learning model. Statistical analysis shows the datatypes are compatible, with a blended-species model reaching ∼95% accuracy and F1 score, maintaining performance while additional human data is collected.

Pharmacokinetics of Budesonide Oral Suspension in Children and Adolescents With Eosinophilic Esophagitis.

The pharmacokinetic (PK) profile of budesonide oral suspension (BOS) was evaluated during a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in pediatric patients with eosinophilic esophagitis (EoE) (MPI 101-01/NCT00762073). Non-compartmental methods were used to calculate PK parameters in 37 patients after receiving morning doses of BOS, with volume and dose adjusted for age (low dose: 0.35 or 0.5 mg; high dose: 1.4 or 2.0 mg [2-9 or 10-18 years old, respectively]). Relationships between apparent oral clearance and volume of distribution, and bodyweight and body mass index were also evaluated. Budesonide systemic exposure increased with BOS dose. After oral administration, time to maximum plasma budesonide concentration occurred ~1 hour post dose and the half-life of budesonide was 3.3-3.5 hours. PK parameters were similar between age groups for low- and high-dose BOS, indicating that volume and dose adjustments for age were appropriate for pediatric patients with EoE. BOS was well tolerated.

Establishment of Host-Algal Endosymbioses: Genetic Response to Symbiont Versus Prey in a Sponge Host.

The freshwater sponge Ephydatia muelleri and its Chlorella-like algal partner is an emerging model for studying animal: algal endosymbiosis. The sponge host is a tractable laboratory organism, and the symbiotic algae are easily cultured. We took advantage of these traits to interrogate questions about mechanisms that govern the establishment of durable intracellular partnerships between hosts and symbionts in facultative symbioses. We modified a classical experimental approach to discern the phagocytotic mechanisms that might be co-opted to permit persistent infections, and identified genes differentially expressed in sponges early in the establishment of endosymbiosis. We exposed algal-free E. muelleri to live native algal symbionts and potential food items (bacteria and native heat-killed algae), and performed RNA-Seq to compare patterns of gene expression among treatments. We found a relatively small but interesting suite of genes that are differentially expressed in the host exposed to live algal symbionts, and a larger number of genes triggered by host exposure to heat-killed algae. The upregulated genes in sponges exposed to live algal symbionts were mostly involved in endocytosis, ion transport, metabolic processes, vesicle-mediated transport, and oxidation-reduction. One of the host genes, an ATP-Binding Cassette transporter that is downregulated in response to live algal symbionts, was further evaluated for its possible role in the establishment of the symbiosis. We discuss the gene expression profiles associated with host responses to living algal cells in the context of conditions necessary for long-term residency within host cells by phototrophic symbionts as well as the genetic responses to sponge phagocytosis and immune-driven pathways.

Gluten Degradation, Pharmacokinetics, Safety, and Tolerability of TAK-062, an Engineered Enzyme to Treat Celiac Disease.

BACKGROUND AND AIMS: Celiac disease (CeD) is an immune-mediated disorder triggered by the ingestion of gluten. Despite adhering to a gluten-free diet (the only management option available to patients with CeD), many patients continue to experience symptoms and intestinal injury. Degradation of immunogenic fractions of gluten peptides in the stomach has been proposed as an approach to reduce toxicity of ingested gluten; however, no enzymes evaluated to date have demonstrated sufficient gluten degradation in complex meals. TAK-062 is a novel, computationally designed endopeptidase under development for the treatment of patients with CeD. METHODS: Pharmacokinetics, safety, and tolerability of TAK-062 100-900 mg were evaluated in a phase I dose escalation study in healthy participants and patients with CeD. Gluten degradation by TAK-062 was evaluated under simulated gastric conditions in vitro and in healthy participants in the phase I study, with and without pretreatment with a proton pump inhibitor. Residual gluten (collected through gastric aspiration in the phase I study) was quantified using R5 and G12 monoclonal antibody enzyme-linked immunosorbent assays. RESULTS: In vitro, TAK-062 degraded more than 99% of gluten (3 g and 9 g) within 10 minutes. In the phase I study, administration of TAK-062 was well tolerated and resulted in a median gluten degradation ranging from 97% to more than 99% in complex meals containing 1-6 g gluten at 20-65 minutes postdose. CONCLUSIONS: TAK-062 is well tolerated and rapidly and effectively degrades large amounts of gluten, supporting the development of this novel enzyme as an oral therapeutic for patients with CeD. (ClinicalTrials.gov: NCT03701555, https://clinicaltrials.gov/ct2/show/NCT03701555.).

Freshwater sponge hosts and their green algae symbionts: a tractable model to understand intracellular symbiosis.

In many freshwater habitats, green algae form intracellular symbioses with a variety of heterotrophic host taxa including several species of freshwater sponge. These sponges perform important ecological roles in their habitats, and the poriferan:green algae partnerships offers unique opportunities to study the evolutionary origins and ecological persistence of endosymbioses. We examined the association between Ephydatia muelleri and its chlorophyte partner to identify features of host cellular and genetic responses to the presence of intracellular algal partners. Chlorella-like green algal symbionts were isolated from field-collected adult E. muelleri tissue harboring algae. The sponge-derived algae were successfully cultured and subsequently used to reinfect aposymbiotic E. muelleri tissue. We used confocal microscopy to follow the fate of the sponge-derived algae after inoculating algae-free E. muelleri grown from gemmules to show temporal patterns of symbiont location within host tissue. We also infected aposymbiotic E. muelleri with sponge-derived algae, and performed RNASeq to study differential expression patterns in the host relative to symbiotic states. We compare and contrast our findings with work in other systems (e.g., endosymbiotic Hydra) to explore possible conserved evolutionary pathways that may lead to stable mutualistic endosymbioses. Our work demonstrates that freshwater sponges offer many tractable qualities to study features of intracellular occupancy and thus meet criteria desired for a model system.

Technical Considerations for Use of Oligonucleotide Solution API.

The most common approach for the manufacture of oligonucleotides includes isolation of the active pharmaceutical ingredient (API) via lyophilization to provide a solid product, which is then dissolved to provide an aqueous formulation. It is well known from the development and manufacture of large molecules ("biologics") that API production does not always require isolation of solid API before drug product formulation, and this article provides technical considerations for the analogous use of oligonucleotide API in solution. The primary factor considered is solution stability, and additional factors such as viscosity, concentration, end-to-end manufacturing, microbiological control, packaging, and storage are also discussed. The technical considerations discussed in this article will aid the careful evaluation of the relative advantages and disadvantages of solution versus powder API for a given oligonucleotide drug substance.

Belonging and exclusion in the lives of young people with intellectual disability in small town communities.

In recent policies, it is assumed that communities welcome the inclusion of young people with intellectual disability. However, little is known about perspectives of young people themselves. This article reports on research that sought to address this gap. Young people with intellectual disability living in three Australian small town communities participated in pictorial mapping and photo-rich methods to explore belonging and exclusion and links between these. Young people's feelings of comfort and safety with local spaces and people were important for their sense of belonging. Emplaced relationships with family and some friends were key to strong belonging, as were positive attachments to disability support workers and spaces. Social exclusion, either from particular places or more generally, was keenly felt. Young people's confidence, willingness to enter social spaces and relationships were magnified by ways that systems responded to their impairment, at worst fracturing their sense of feeling welcome and included.

Assessing the Effect of Middle Ear Effusions on Wideband Acoustic Immittance Using Optical Coherence Tomography.

OBJECTIVES: Wideband acoustic immittance (WAI) noninvasively assesses middle ear function by measuring the sound conduction over a range of audible frequencies. Although several studies have shown the potential of WAI for detecting the presence of middle ear effusions (MEEs), determining the effects of MEE type and amount on WAI in vivo has been challenging due to the anatomical location of middle ear cavity. The purpose of this study is to correlate WAI measurements with physical characteristics of the middle ear and MEEs determined by optical coherence tomography (OCT), a noninvasive optical imaging technique. DESIGN: Sixteen pediatric subjects (average age of 7 ± 4 years) were recruited from the primary care clinic at Carle Foundation Hospital (Urbana, IL). A total of 22 ears (normal: 15 ears, otitis media with effusion: 6 ears, and acute otitis media: 1 ear, based on physician's diagnosis) were examined via standard otoscopy, tympanometry, OCT imaging, and WAI measurements in a busy, community-based clinical setting. Cross-sectional OCT images were analyzed to quantitatively assess the presence, type (relative turbidity based on the amount of scattering), and amount (relative fluid level) of MEEs. These OCT metrics were utilized to categorize subject ears into no MEE (control), biofilm without a MEE, serous-scant, serous-severe, mucoid-scant, and mucoid-severe MEE groups. The absorbance levels in each group were statistically evaluated at α = 0.05. RESULTS: The absorbance of the control group showed a similar trend when compared with a pediatric normative dataset, and the presence of an MEE generally decreased the power absorbance. The mucoid MEE group showed significantly less power absorbance from 2.74 to 4.73 kHz (p < 0.05) when compared with the serous MEE group, possibly due to the greater mass impeding the middle ear system. Similarly, the greater amount of middle ear fluid contributed to the lower power absorbance from 1.92 to 2.37 kHz (p< 0.05), when compared with smaller amounts of fluid. As expected, the MEEs with scant fluid only significantly affected the power absorbance at frequencies greater than 4.85 kHz. A large variance in the power absorbance was observed between 2 and 5 kHz, suggesting the dependence on both the type and amount of MEE. CONCLUSIONS: Physical characteristics of the middle ear and MEEs quantified from noninvasive OCT images can be helpful to understand abnormal WAI measurements. Mucoid MEEs decrease the power absorbance more than serous MEEs, and the greater amounts of MEE decreases the power absorbance, especially at higher (>2 kHz) frequencies. As both the type and amount of MEE can significantly affect WAI measurements, further investigations to correlate acoustic measurements with physical characteristics of middle ear conditions in vivo is needed.

Automated classification platform for the identification of otitis media using optical coherence tomography.

The diagnosis and treatment of otitis media (OM), a common childhood infection, is a significant burden on the healthcare system. Diagnosis relies on observer experience via otoscopy, although for non-specialists or inexperienced users, accurate diagnosis can be difficult. In past studies, optical coherence tomography (OCT) has been used to quantitatively characterize disease states of OM, although with the involvement of experts to interpret and correlate image-based indicators of infection with clinical information. In this paper, a flexible and comprehensive framework is presented that automatically extracts features from OCT images, classifies data, and presents clinically relevant results in a user-friendly platform suitable for point-of-care and primary care settings. This framework was used to test the discrimination between OCT images of normal controls, ears with biofilms, and ears with biofilms and middle ear fluid (effusion). Predicted future performance of this classification platform returned promising results (90%+ accuracy) in various initial tests. With integration into patient healthcare workflow, users of all levels of medical experience may be able to collect OCT data and accurately identify the presence of middle ear fluid and/or biofilms.

Secreted frizzled related protein is a target of PaxB and plays a role in aquiferous system development in the freshwater sponge, Ephydatia muelleri.

Canonical and non-canonical Wnt signaling, as well as the Pax/Six gene network, are involved in patterning the freshwater sponge aquiferous system. Using computational approaches to identify transcription factor binding motifs in a freshwater sponge genome, we located putative PaxB binding sites near a Secreted Frizzled Related Protein (SFRP) gene in Ephydatia muelleri. EmSFRP is expressed throughout development, but with highest levels in juvenile sponges. In situ hybridization and antibody staining show EmSFRP expression throughout the pinacoderm and choanoderm in a subpopulation of amoeboid cells that may be differentiating archeocytes. Knockdown of EmSFRP leads to ectopic oscula formation during development, suggesting that EmSFRP acts as an antagonist of Wnt signaling in E. muelleri. Our findings support a hypothesis that regulation of the Wnt pathway by the Pax/Six network as well as the role of Wnt signaling in body plan morphogenesis was established before sponges diverged from the rest of the metazoans.

Ontogeny of symbiont community structure in two carotenoid-rich, viviparous marine sponges: comparison of microbiomes and analysis of culturable pigmented heterotrophic bacteria.

Marine sponges harbour diverse communities of microbes. Mechanisms used to establish microbial symbioses in sponges are poorly understood, and the relative contributions of horizontal and vertical transmission are unknown for most species. We examined microbial communities in adults and larvae of carotenoid-rich Clathria prolifera and Halichondria bowerbanki from the mid-Atlantic region of the eastern United States. We sequenced microbiomes from larvae and their mothers and seawater (16S rRNA gene sequencing), and compared microbial community characteristics between species and ambient seawater. The microbial communities in sponges were significantly different than those found in seawater, and each species harboured a distinctive microbiome. Larval microbiomes exhibited significantly lower richness compared with adults, with both sponges appearing to transfer to larvae a particular subset of the adult microbiome. We also surveyed culturable bacteria isolated from larvae of both species. Due to conspicuous coloration of adults and larvae, we focused on pigmented heterotrophic bacteria. We found that the densities of bacteria, in terms of colony-forming units and pigmented heterotrophic bacteria, were higher in larvae than in seawater. We identified a common mode of transmission (vertical and horizontal) of microbes in both sponges that might differ between species.

European Pharma Oligonucleotide Consortium: A Move to Consolidate Oligonucleotide Knowledge and Share Experience Within the Community.

A consortium of seven pharma companies has been formed with the aim of sharing knowledge on and harmonizing approaches to oligonucleotide development. This letter aims to raise awareness of this new group and to set expectations for future publications.

In vivo detection of nanometer-scale structural changes of the human tympanic membrane in otitis media.

Otitis media (OM) is a common ear infection and a leading cause of conductive hearing loss in the pediatric population. Current technologies such as otoscopy, pneumatic otoscopy, tympanometry, and acoustic reflectometry are used to diagnose OM, which can reasonably diagnose the infection with a sensitivity and specificity of 50-90% and 60-90%, respectively. However, these techniques provide limited information about the physical architecture of the tympanic membrane (TM), or what may lie behind it. Here, we report the detection of nanometer-scale structural changes of the TM using nano-sensitive optical coherence tomography (nsOCT). In total, an image dataset from 65 pediatric subjects from three different groups (normal, acute OM, and chronic OM) and with longitudinal image-based analysis of ear infections were included in this study. The nsOCT data were correlated with physician diagnosis and with OCT thickness measurements and were found to be in good agreement with these results. We report that nsOCT detects in vivo structural deformations of the TM earlier than OCT alone, and enhances the detection sensitivity of OCT measurements. This unique technique for early detection of nano-scale structural modifications in the TM has the potential to aid in our understanding of microbiological effects, and possibly for early diagnosis and more effective treatment of OM.

Pneumatic low-coherence interferometry otoscope to quantify tympanic membrane mobility and middle ear pressure.

Pneumatic otoscopy to assess the mobility of the tympanic membrane (TM) is a highly recommended diagnostic method of otitis media (OM), a widespread middle ear infection characterized by the fluid accumulation in the middle ear. Nonetheless, limited depth perception and subjective interpretation of small TM displacements have challenged the appropriate and efficient examination of TM dynamics experienced during OM. In this paper, a pneumatic otoscope integrated with low coherence interferometry (LCI) was adapted with a controlled pressure-generating system to record the pneumatic response of the TM and to estimate middle ear pressure (MEP). Forty-two ears diagnosed as normal (n = 25), with OM (n = 10), or associated with an upper respiratory infection (URI) (n = 7) were imaged with a pneumatic LCI otoscope with an axial, transverse, and temporal resolution of 6 µm, 20 µm, and 1 msec, respectively. The TM displacement under pneumatic pressure transients (a duration of 0.5 sec with an intensity of ± 150 daPa) was measured to compute two metrics (compliance and amplitude ratio). These metrics were correlated with peak acoustic admittance and MEP from tympanometry and statistically compared via Welch's t-test. As a result, the compliance represents pneumatic TM mobility, and the amplitude ratio estimates MEP. The presence of a middle ear effusion (MEE) significantly decreased compliance (p<0.001). The amplitude ratio of the OM group was statistically less than that of the normal group (p<0.01), indicating positive MEP. Unlike tympanometry, pneumatic LCI otoscopy quantifies TM mobility as well as MEP regardless of MEE presence. With combined benefits of pneumatic otoscopy and tympanometry, pneumatic LCI otoscopy may provide new quantitative metrics for understanding TM dynamics and diagnosing OM.

Sibling species of mutualistic Symbiodinium clade G from bioeroding sponges in the western Pacific and western Atlantic oceans.

Dinoflagellates in the genus Symbiodinium associate with a broad array of metazoan and protistian hosts. Symbiodinium-based symbioses involving bioeroding sponge hosts have received less attention than those involving popular scleractinian hosts. Certain species of common Cliona harbor high densities of an ecologically restricted group of Symbiodinium, referred to as Clade G. Clade G Symbiodinium are also known to form stable and functionally important associations with Foraminifera and black corals (Antipatharia) Analyses of genetic evidence indicate that Clade G likely comprises several distinct species. Here, we use nucleotide sequence data in combination with ecological and geographic attributes to formally describe Symbiodinium endoclionum sp. nov. obtained from the Pacific boring sponge Cliona orientalis and Symbiodinium spongiolum sp. nov. from the congeneric western Atlantic sponge Cliona varians. These species appear to be part of an adaptive radiation comprising lineages of Clade G specialized to the metazoan phyla Porifera and Cnidaria, which began prior to the separation of the Pacific and Atlantic Oceans.

Psychometric validation of the Dysphagia Symptom Questionnaire in patients with eosinophilic esophagitis treated with budesonide oral suspension.

BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by high levels of eosinophils in the esophageal mucosa. Patients with the disease present with a range of symptoms, including dysphagia (difficulty swallowing). The aim of this analysis was to assess the psychometric properties of the Dysphagia Symptom Questionnaire (DSQ), a patient-reported outcome (PRO) measure of dysphagia associated with EoE. Psychometric properties of the DSQ were assessed using data collected from a 12-week, phase 2, multicenter, randomized, double-blind, placebo-controlled trial of budesonide oral suspension in adolescents and adults (11-40 years old) with EoE. RESULTS: The study population comprised 93 patients with EoE; 94.6% of whom were white, 68.8% were male and the mean age (standard deviation) was 21.6 (7.7) years. Patients had been diagnosed with EoE for a mean of 37.6 months before study initiation. The DSQ was feasible to implement with few item-level data missing at baseline. Item discrimination was high, with floor and ceiling effects below the predefined threshold (≤9%). Higher DSQ scores corresponded with presence and increased severity of dysphagia, indicative of strong item discrimination among patients at baseline (threshold >50%). The DSQ was able to detect changes in symptoms over time and produced similar outcomes to those from physician- and other patient-rated measures, supportive of construct validity. The DSQ had strong test-retest reliability (intraclass correlation coefficient, r = 0.82); and was also responsive to disease-level changes, with higher DSQ scores corresponding to increased esophageal eosinophilic burden. Lastly, the percentage changes in the minimal clinically important difference and clinically important difference in DSQ score were estimated at -27.4% and -55.4%, respectively. CONCLUSIONS: These analyses support the DSQ as a valid and reliable measure of dysphagia in patients with EoE. Changes in DSQ scores suggest a level of agreement between clinician, patient and histologic response. The DSQ should therefore be considered a viable PRO measure of dysphagia for use in future therapeutic studies of EoE.

Micro- and nano-structural characterization of six marine sponges of the class Demospongiae.

The sponges produce their skeletal elements and silicateins are the key enzymes in this process. The mechanism underlying the formation of their silica skeleton and its structural properties are of exceptional interest for applications in technology. Micro- and nano-scale structural analysis of the six marine sponges belonging to Demospongiae [Callyspongia (Cladochalia) plicifera (Lamarck, 1814), Cervicornia cuspidifera (Lamarck, 1815), Cinachyrela sp., Niphates erecta (Duchassaing and Michelotti, 1864), Xestospongia muta (Schmidt, 1870) and Amphimedon compressa (Duchassaing and Michelotti, 1864)] were carried out by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) and Small-Angle X-ray Scattering (SAXS) techniques. The nano-structural characterizations give some informative evidence about the manner in which silica/silicatein in spicule skeletons is produced by the sponges. The sponge species were successfully discriminated using cluster analysis (HCA) based on FTIR spectra. This study demonstrates and detection of structural differences among sponges and their spicules using combined techniques.

Noninvasive depth-resolved optical measurements of the tympanic membrane and middle ear for differentiating otitis media.

OBJECTIVE/HYPOTHESIS: In this study, optical coherence tomography (OCT) is used to noninvasively and quantitatively determine tympanic membrane (TM) thickness and the presence and thickness of any middle-ear biofilm located behind the TM. These new metrics offer the potential to differentiate normal, acute, and chronic otitis media (OM) infections in pediatric subjects. STUDY DESIGN: Case series with comparison group. METHODS: The TM thickness of 34 pediatric subjects was acquired using a custom-built, handheld OCT system following a traditional otoscopic ear exam. RESULTS: Overall thickness (TM and any associated biofilm) was shown to be statistically different for normal, acute, and chronic infection groups (normal-acute and normal-chronic: P value < 0.001; acute-chronic: P value = 0.0016). Almost all observed scans from the chronic group had an accompanying biofilm structure. When the thickness of the TM and biofilm were considered separately in chronic OM, the chronic TM thickness correlated with the normal group (P value = 0.68) yet was still distinct from the acute OM group (P value < 0.001), indicating that the TM in chronic OM returns to relatively normal thickness levels. CONCLUSION: Identifying these physical changes in vivo provides new metrics for noninvasively and quantitatively differentiating normal, acute, and chronic OM. This new diagnostic information has the potential to assist physicians to more effectively and efficiently screen, manage, and refer patients based on quantitative data. LEVEL OF EVIDENCE: 4.

Production possibility frontiers in phototroph:heterotroph symbioses: trade-offs in allocating fixed carbon pools and the challenges these alternatives present for understanding the acquisition of intracellular habitats.

Intracellular habitats have been invaded by a remarkable diversity of organisms, and strategies employed to successfully reside in another species' cellular space are varied. Common selective pressures may be experienced in symbioses involving phototrophic symbionts and heterotrophic hosts. Here I refine and elaborate the Arrested Phagosome Hypothesis that proposes a mechanism that phototrophs use to gain access to their host's intracellular habitat. I employ the economic concept of production possibility frontiers (PPF) as a useful heuristic to clearly define the trade-offs that an intracellular phototroph is likely to face as it allocates photosynthetically-derived pools of energy. Fixed carbon can fuel basic metabolism/respiration, it can support mitotic division, or it can be translocated to the host. Excess photosynthate can be stored for future use. Thus, gross photosynthetic productivity can be divided among these four general categories, and natural selection will favor phenotypes that best match the demands presented to the symbiont by the host cellular habitat. The PPF highlights trade-offs that exist between investment in growth (i.e., mitosis) or residency (i.e., translocating material to the host). Insights gained from this perspective might help explain phenomena such as coral bleaching because deficits in photosynthetic production are likely to diminish a symbiont's ability to "afford" the costs of intracellular residency. I highlight deficits in our current understanding of host:symbiont interactions at the molecular, genetic, and cellular level, and I also discuss how semantic differences among scientists working with different symbiont systems may diminish the rate of increase in our understanding of phototrophic-based associations. I argue that adopting interdisciplinary (in this case, inter-symbiont-system) perspectives will lead to advances in our general understanding of the phototrophic symbiont's intracellular niche.