On the evolutionary developmental biology of the cell.

Organisms are complex assemblages of cells, cells that produce light, shoot harpoons, and secrete glue. Therefore, identifying the mechanisms that generate novelty at the level of the individual cell is essential for understanding how multicellular life evolves. For decades, the field of evolutionary developmental biology (Evo-Devo) has been developing a framework for connecting genetic variation that arises during embryonic development to the emergence of diverse adult forms. With increasing access to new single cell 'omics technologies and an array of techniques for manipulating gene expression, we can now extend these inquiries inward to the level of the individual cell. In this opinion, I argue that applying an Evo-Devo framework to single cells makes it possible to explore the natural history of cells, where this was once only possible at the organismal level.

Patients' experiences of living with low anterior resection syndrome three to six months after colorectal cancer surgery: A phenomenological study.

BACKGROUND: Increased use of sphincter-preserving surgery following colorectal cancer has led to more people living with low anterior resection syndrome (LARS), a disordered bowel function that significantly impacts quality of life. Little is known about how patients experience the first months following sphincter-preserving surgery and having LARS. OBJECTIVE: To shed light on what it means to live with LARS in the first three to six months after colorectal cancer sphincter-preserving surgery. METHOD: A qualitative study with a phenomenological approach constitutes the study design. Semi-structured interviews were conducted with five participants from September 2022 to January 2023. The transcribed interviews were analysed using Giorgi's phenomenological method. RESULTS: Five themes emerged from the analysis: bowel emptying becomes all-consuming and affects both daily life and working life, you hear what they're saying, but don't understand what it means until your body goes through it, low anterior resection syndrome may impact sexual life, leaving feelings of guilt, it doesn't matter what the circumstances are, but rather how one deals with them, and support and follow-up from healthcare professionals, employers, family and friends are crucial for living a good life with LARS. CONCLUSION: Participants described struggles living with major LARS in the early period following hospital discharge. However, few months later, they had developed strategies enabling them to control their everyday life. Support and follow-up from healthcare professionals, employers, family, and friends were crucial when learning to live with major LARS. Participants expressed desire for a systematic and proactive follow-up from healthcare professionals and contact with peer-support groups.

Morphological and dietary changes encoded in the genome of Beroe ovata, a ctenophore-eating ctenophore.

As the sister group to all other animals, ctenophores (comb jellies) are important for understanding the emergence and diversification of numerous animal traits. Efforts to explore the evolutionary processes that promoted diversification within Ctenophora are hindered by undersampling genomic diversity within this clade. To address this gap, we present the sequence, assembly and initial annotation of the genome of Beroe ovata. Beroe possess unique morphology, behavior, ecology and development. Unlike their generalist carnivorous kin, beroid ctenophores feed exclusively on other ctenophores. Accordingly, our analyses revealed a loss of chitinase, an enzyme critical for the digestion of most non-ctenophore prey, but superfluous for ctenophorivores. Broadly, our genomic analysis revealed that extensive gene loss and changes in gene regulation have shaped the unique biology of B. ovata. Despite the gene losses in B. ovata, our phylogenetic analyses on photosensitive opsins and several early developmental regulatory genes show that these genes are conserved in B. ovata. This additional sampling contributes to a more complete reconstruction of the ctenophore ancestor and points to the need for extensive comparisons within this ancient and diverse clade of animals. To promote further exploration of these data, we present BovaDB (http://ryanlab.whitney.ufl.edu/bovadb/), a portal for the B. ovata genome.

Detection of delirium in older patients-A point prevalence study in surgical and non-surgical hospital wards.

AIMS AND OBJECTIVES: To (i) determine the prevalence of delirium and identify delirium subtypes in surgical and non-surgical patients aged ≥65 years, (ii) determine whether certain precipitating factors affect the prevalence of delirium and (iii) review patients' medical records for description of delirium symptoms and the presence of International Classification of Diseases (ICD-10) coding for delirium in discharge summaries. METHODOLOGICAL DESIGN AND JUSTIFICATIONS: Despite being a robust predictor of morbidity and mortality in older adults, delirium might be inadequately recognised and under-reported in patients' medical records and discharge summaries. A point prevalence study (24-h) of patients ≥65 years from surgical and non-surgical wards was therefore conducted in a tertiary university hospital. ETHICAL ISSUES AND APPROVAL: The study was approved by the Data Protection Officer at the university hospital (2018/3454). RESEARCH METHODS, INSTRUMENTS AND/OR INTERVENTIONS: Patients were assessed for delirium with 4AT and delirium subtypes with the Delirium Motor Subtype Scale. Information about room transfers, need and use of sensory aids and medical equipment was collected onsite. Patients' medical records were reviewed for description of delirium symptoms and of ICD-10 codes. RESULTS: Overall, 123 patients were screened (52% female). Delirium was identified in 27% of them. Prevalence was associated with advanced age (≥85 years). The uncharacterised delirium subtype was most common (36%), followed by hypoactive (30%), hyperactive (24%) and mixed (9%). There were significant associations between positive screening tests and the need and use of sensory aids. Delirium symptoms were described in 58% of the patients who tested positive for delirium and the ICD-10 code for delirium was registered in 12% of these patients' discharge summaries. CONCLUSIONS: The high prevalence of delirium and limited use of discharge codes highlight the need to improve the identification of delirium in hospital settings and at discharge. Increased awareness and detection of delirium in hospital settings are vital to improve patient care.

A multimodality review of gynecologic devices in the pelvis.

There are a wide variety of gynecologic devices encountered on pelvic imaging which may not be the focus or primary reason for imaging. Such devices include pessaries, menstrual products, radiation therapy devices, tubal occlusion devices, and contraceptive devices, including intrauterine devices and intravaginal rings. This manuscript offers a comprehensive review of multimodality imaging appearances of gynecologic devices encountered on pelvic imaging and discusses device indications, positioning, and complications.

Socioeconomic Disparities and Emergency Department Visits for Diabetic Retinopathy in California.

Purpose: To investigate the association between neighborhood-level socioeconomic factors, quantified by the Distressed Communities Index, and emergency department visits for diabetic retinopathy (DR). Methods: All patients who presented to the emergency department for DR in California were analyzed using the State Emergency Department Database (2018-2020). Patients were stratified by Distressed Communities Index score and DR severity. Logistic regression was applied to explore the independent correlation between Distressed Communities Index scores and proliferative DR (PDR). Results: Of 2 725 195 emergency department visits for diabetic patients, Distressed Communities Index data were available for 2 459 577 (90.3%); 39 693 were for DR, including 13 617 (34.3%) for PDR. Hispanics (44.2%) were the largest racial/ethnic group to present for PDR, followed by non-Hispanic Whites (19.6%) and non-Hispanic Blacks (19.3%). A significant association was observed between the Distressed Communities Index and emergency department visits for PDR, with distressed neighborhoods having the highest incidence (adjusted odds ratio [aOR], 1.63; 95% CI, 1.20-2.23; P = .001). Other predictors included Hispanic ethnicity (aOR, 2.21; 95% CI, 1.97-2.48; P < .001) and Black race (aOR, 1.46; 95% CI, 1.28-1.67; P < .001) compared with White race and having Medicaid (aOR, 1.37; 95% CI, 1.13-1.65; P = .001) compared with private insurance. Conclusions: The Distressed Communities Index identified patients residing in the most distressed neighborhoods as being at the highest risk for presenting to the emergency department for PDR based on 7 socioeconomic factors. Policymakers may consider the Distressed Communities Index as a tool for targeting DR prevention strategies and improving healthcare accessibility.

The Adverse Event Landscape of Stem Cell Transplant: Evidence for aGVHD Driving Early Transplant Associated Toxicities.

Although unrelated-donor (URD) hematopoietic cell transplantation (HCT) is associated with many toxicities, a detailed analysis of adverse events, as defined by the Common Terminology Criteria for Adverse Events (CTCAE), has not previously been curated. This represents a major unmet need, especially as it relates to assessing the safety of novel agents. We analyzed a detailed AE database from the "ABA2" randomized, double-blind, placebo-controlled clinical trial of abatacept for acute graft-versus-host disease (aGVHD) prevention, for which the FDA mandated a detailed AE assessment through Day +180, and weekly neutrophil and platelet counts through Day +100. These were analyzed for their relationship to key transplant outcomes, with a major focus on the impact of aGVHD on the development/severity of AEs. A total of 2102 AEs and 1816 neutrophil/platelet counts were analyzed from 142 8/8-HLA-matched URD HCT recipients on ABA2 (placebo cohort, n = 69, abatacept cohort, n = 73). This analysis resulted in 2 major observations. (1) Among graft source, conditioning intensity, age, and Grade 2 to 4 aGVHD, only aGVHD impacted Grade 3 to 5 AE acquisition after the first month post-transplant. (2) The development of Grade 3 to 4 aGVHD was associated with thrombocytopenia. We have created a detailed resource for the transplant community by which to contextualize clinical toxicities after transplant. It has identified aGVHD as a major driver of post-HCT Grade 3 to 5 AEs, and underscored a link between aGVHD and thrombocytopenia. This establishes a critical safety framework upon which the impact of novel post-transplant aGVHD therapeutics should be evaluated. This trial was registered at www.clinicaltrials.gov (#NCT01743131).

Climate change and its impact on asthma.

ABSTRACT: Earth's climate is changing at an unprecedented pace, primarily due to anthropogenic causes including greenhouse gas emissions. Evidence shows a strong link between climate change and its effects on asthma. Healthcare professionals must be educated to advocate for and lead effective strategies to reduce the health risks of climate change.

B-cell-directed CAR T-cell therapy activates CD8+ cytotoxic CARneg bystander T cells in patients and nonhuman primates.

ABSTRACT: Chimeric antigen receptor (CAR) T cells hold promise as a therapy for B-cell-derived malignancies, and despite their impressive initial response rates, a significant proportion of patients ultimately experience relapse. Although recent studies have explored the mechanisms of in vivo CAR T-cell function, little is understood about the activation of surrounding CARneg bystander T cells and their potential to enhance tumor responses. We performed single-cell RNA sequencing on nonhuman primate (NHP) and patient-derived T cells to identify the phenotypic and transcriptomic hallmarks of bystander activation of CARneg T cells following B-cell-targeted CAR T-cell therapy. Using a highly translatable CD20 CAR NHP model, we observed a distinct population of activated CD8+ CARneg T cells emerging during CAR T-cell expansion. These bystander CD8+ CARneg T cells exhibited a unique transcriptional signature with upregulation of natural killer-cell markers (KIR3DL2, CD160, and KLRD1), chemokines, and chemokine receptors (CCL5, XCL1, and CCR9), and downregulation of naïve T-cell-associated genes (SELL and CD28). A transcriptionally similar population was identified in patients after a tisagenlecleucel infusion. Mechanistic studies revealed that interleukin-2 (IL-2) and IL-15 exposure induced bystander-like CD8+ T cells in a dose-dependent manner. In vitro activated and patient-derived T cells with a bystander phenotype efficiently killed leukemic cells through a T-cell receptor-independent mechanism. Collectively, to our knowledge, these data provide the first comprehensive identification and profiling of CARneg bystander CD8+ T cells following B-cell-targeting CAR T-cell therapy and suggest a novel mechanism through which CAR T-cell infusion might trigger enhanced antileukemic responses. Patient samples were obtained from the trial #NCT03369353, registered at www.ClinicalTrials.gov.

How Do Persons Who Inject Drugs Experience Care From Nurses in Hospital Settings? A Qualitative Study.

People who inject drugs (PWID) are at increased risk of acute and chronic health outcomes and in need of in-hospital healthcare services. This study aims to give insight into how PWID experience care from nurses in hospital settings. We used a qualitative descriptive design and applied reflexive thematic analysis to 11 individual semi-structured interviews with PWID. Our analysis generated the following main themes: (1) diminishment and distance-always just a drug addict, (2) gratitude-equal care not taken for granted, and (3) vulnerability-already carrying a heavy burden. Our findings reveal a complex, nuanced narrative regarding participants' experiences of nursing care and highlight the importance of enhancing knowledge, understanding, empathy, and communication skills when nurses encounter PWID. Our research suggests that patients' vulnerability resulting from previous experiences defined their perception of quality of care. Insight from this study provides valuable knowledge about how to enhance nursing care for PWID.

Proinsulin folding and trafficking defects trigger a common pathological disturbance of endoplasmic reticulum homeostasis.

Primary defects in folding of mutant proinsulin can cause dominant-negative proinsulin accumulation in the endoplasmic reticulum (ER), impaired anterograde proinsulin trafficking, perturbed ER homeostasis, diminished insulin production, and ß-cell dysfunction. Conversely, if primary impairment of ER-to-Golgi trafficking (which also perturbs ER homeostasis) drives misfolding of nonmutant proinsulin-this might suggest bi-directional entry into a common pathological phenotype (proinsulin misfolding, perturbed ER homeostasis, and deficient ER export of proinsulin) that can culminate in diminished insulin storage and diabetes. Here, we've challenged ß-cells with conditions that impair ER-to-Golgi trafficking, and devised an accurate means to assess the relative abundance of distinct folded/misfolded forms of proinsulin using a novel nonreducing SDS-PAGE/immunoblotting protocol. We confirm abundant proinsulin misfolding upon introduction of a diabetogenic INS mutation, or in the islets of db/db mice. Whereas blockade of proinsulin trafficking in Golgi/post-Golgi compartments results in intracellular accumulation of properly-folded proinsulin (bearing native disulfide bonds), impairment of ER-to-Golgi trafficking (regardless whether such impairment is achieved by genetic or pharmacologic means) results in decreased native proinsulin with more misfolded proinsulin. Remarkably, reversible ER-to-Golgi transport defects (such as treatment with brefeldin A or cellular energy depletion) upon reversal quickly restore the ER folding environment, resulting in the disappearance of pre-existing misfolded proinsulin while preserving proinsulin bearing native disulfide bonds. Thus, proper homeostatic balance of ER-to-Golgi trafficking is linked to a more favorable proinsulin folding (as well as trafficking) outcome.

Tubular CPT1A deletion minimally affects aging and chronic kidney injury.

Kidney tubules use fatty acid oxidation (FAO) to support their high energetic requirements. Carnitine palmitoyltransferase 1A (CPT1A) is the rate-limiting enzyme for FAO, and it is necessary to transport long-chain fatty acids into mitochondria. To define the role of tubular CPT1A in aging and injury, we generated mice with tubule-specific deletion of Cpt1a (Cpt1aCKO mice), and the mice were either aged for 2 years or injured by aristolochic acid or unilateral ureteral obstruction. Surprisingly, Cpt1aCKO mice had no significant differences in kidney function or fibrosis compared with wild-type mice after aging or chronic injury. Primary tubule cells from aged Cpt1aCKO mice had a modest decrease in palmitate oxidation but retained the ability to metabolize long-chain fatty acids. Very-long-chain fatty acids, exclusively oxidized by peroxisomes, were reduced in kidneys lacking tubular CPT1A, consistent with increased peroxisomal activity. Single-nuclear RNA-Seq showed significantly increased expression of peroxisomal FAO enzymes in proximal tubules of mice lacking tubular CPT1A. These data suggest that peroxisomal FAO may compensate in the absence of CPT1A, and future genetic studies are needed to confirm the role of peroxisomal ß-oxidation when mitochondrial FAO is impaired.

Alloengraftment without significant toxicity or GVHD in CD45 antibody-drug conjugate-conditioned Fanconi anemia mice.

ABSTRACT: Fanconi anemia (FA) is an inherited DNA repair disorder characterized by bone marrow (BM) failure, developmental abnormalities, myelodysplasia, leukemia, and solid tumor predisposition. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a mainstay treatment, is limited by conditioning regimen-related toxicity and graft-versus-host disease (GVHD). Antibody-drug conjugates (ADCs) targeting hematopoietic stem cells (HSCs) can open marrow niches permitting donor stem cell alloengraftment. Here, we report that single dose anti-mouse CD45-targeted ADC (CD45-ADC) facilitated stable, multilineage chimerism in 3 distinct FA mouse models representing 90% of FA complementation groups. CD45-ADC profoundly depleted host stem cell enriched Lineage-Sca1+cKit+ cells within 48 hours. Fanca-/- recipients of minor-mismatched BM and single dose CD45-ADC had peripheral blood (PB) mean donor chimerism >90%; donor HSCs alloengraftment was verified in secondary recipients. In Fancc-/- and Fancg-/- recipients of fully allogeneic grafts, PB mean donor chimerism was 60% to 80% and 70% to 80%, respectively. The mean percent donor chimerism in BM and spleen mirrored PB results. CD45-ADC-conditioned mice did not have clinical toxicity. A transient <2.5-fold increase in hepatocellular enzymes and mild-to-moderate histopathological changes were seen. Under GVHD allo-HSCT conditions, wild-type and Fanca-/- recipients of CD45-ADC had markedly reduced GVHD lethality compared with lethal irradiation. Moreover, single dose anti-human CD45-ADC given to rhesus macaque nonhuman primates on days -6 or -10 was at least as myeloablative as lethal irradiation. These data suggest that CD45-ADC can potently promote donor alloengraftment and hematopoiesis without significant toxicity or severe GVHD, as seen with lethal irradiation, providing strong support for clinical trial considerations in highly vulnerable patients with FA.

Linking Type and Extent of Head Trauma to Cavum Septum Pellucidum in Older Adults With and Without Alzheimer Disease and Related Dementias.

BACKGROUND AND OBJECTIVES: Cavum septum pellucidum (CSP) is a common but nonspecific MRI finding in individuals with prior head trauma. The type and extent of head trauma related to CSP, CSP features specific to head trauma, and the impact of brain atrophy on CSP are unknown. We evaluated CSP cross-sectionally and longitudinally in healthy and clinically impaired older adults who underwent detailed lifetime head trauma characterization. METHODS: This is an observational cohort study of University of California, San Francisco Memory and Aging Center participants (healthy controls [HCs], those with Alzheimer disease or related dementias [ADRDs], subset with traumatic encephalopathy syndrome [TES]). We characterized traumatic brain injury (TBI) and repetitive head impacts (RHI) through contact/collision sports. Study groups were no RHI/TBI, prior TBI only, prior RHI only, and prior RHI + TBI. We additionally looked within TBI (1, 2, or 3+) and RHI (1-4, 5-10, and 11+ years). All underwent baseline MRI, and 67% completed a second MRI (median follow-up = 5.4 years). CSP measures included grade (0-4) and length (millimeters). Groups were compared on likelihood of CSP (logistic regression, odds ratios [ORs]) and whether CSP length discriminated groups (area under the curve [AUC]). RESULTS: Our sample included 266 participants (N = 160 HCs, N = 106 with ADRD or TES; age 66.8 ± 8.2 years, 45.3% female). Overall, 123 (49.8%) participants had no RHI/TBI, 52 (21.1%) had TBI only, 41 (16.6%) had RHI only, 31 (12.6%) had RHI + TBI, and 20 were classified as those with TES (7.5%). Compared with no RHI/TBI, RHI + TBI (OR 3.11 [1.23-7.88]) and TES (OR 11.6 [2.46-54.8]) had greater odds of CSP. Approximately 5-10 years (OR 2.96 [1.13-7.77]) and 11+ years of RHI (OR 3.14 [1.06-9.31]) had higher odds of CSP. CSP length modestly discriminated participants with 5-10 years (AUC 0.63 [0.51-0.75]) and 11+ years of prior RHI (AUC 0.69 [0.55-0.84]) from no RHI/TBI (cut point = 6 mm). Strongest effects were noted in analyses of American football participation. Longitudinally, CSP grade was unchanged in 165 (91.7%), and length was unchanged in 171 (95.5%) participants. DISCUSSION: Among older adults with and without neurodegenerative disease, risk of CSP is driven more by duration (years) of RHI, especially American football, than number of TBI. CSP length (≥6 mm) is relatively specific to individuals who have had substantial prior RHI. Neurodegenerative disease and progressive atrophy do not clearly influence development or worsening of CSP.

Genome-matched treatments and patient outcomes in the Maine Cancer Genomics Initiative (MCGI).

Genomic tumor testing (GTT) is an emerging technology aimed at identifying variants in tumors that can be targeted with genomically matched drugs. Due to limited resources, rural patients receiving care in community oncology settings may be less likely to benefit from GTT. We analyzed GTT results and observational clinical outcomes data from patients enrolled in the Maine Cancer Genomics Initiative (MCGI), which provided access to GTTs; clinician educational resources; and genomic tumor boards in community practices in a predominantly rural state. 1603 adult cancer patients completed enrollment; 1258 had at least one potentially actionable variant identified. 206 (16.4%) patients received a total of 240 genome matched treatments, of those treatments, 64% were FDA-approved in the tumor type, 27% FDA-approved in a different tumor type and 9% were given on a clinical trial. Using Inverse Probability of Treatment Weighting to adjust for baseline characteristics, a Cox proportional hazards model demonstrated that patients who received genome matched treatment were 31% less likely to die within 1 year compared to those who did not receive genome matched treatment (HR: 0.69; 95% CI: 0.52-0.90; p-value: 0.006). Overall, GTT through this initiative resulted in levels of genome matched treatment that were similar to other initiatives, however, clinical trials represented a smaller share of treatments than previously reported, and "off-label" treatments represented a greater share. Although this was an observational study, we found evidence for a potential 1-year survival benefit for patients who received genome matched treatments. These findings suggest that when disseminated and implemented with a supportive infrastructure, GTT may benefit cancer patients in rural community oncology settings, with further work remaining on providing genome-matched clinical trials.

Multiplexed Functional Assessments of MYH7 Variants in Human Cardiomyocytes.

BACKGROUND: Pathogenic autosomal-dominant missense variants in MYH7 (myosin heavy chain 7), which encodes the sarcomeric protein (ß-MHC [beta myosin heavy chain]) expressed in cardiac and skeletal myocytes, are a leading cause of hypertrophic cardiomyopathy and are clinically actionable. However, ≈75% of MYH7 missense variants are of unknown significance. While human-induced pluripotent stem cells (hiPSCs) can be differentiated into cardiomyocytes to enable the interrogation of MYH7 variant effect in a disease-relevant context, deep mutational scanning has not been executed using diploid hiPSC derivates due to low hiPSC gene-editing efficiency. Moreover, multiplexable phenotypes enabling deep mutational scanning of MYH7 variant hiPSC-derived cardiomyocytes are unknown. METHODS: To overcome these obstacles, we used CRISPRa On-Target Editing Retrieval enrichment to generate an hiPSC library containing 113 MYH7 codon variants suitable for deep mutational scanning. We first established that ß-MHC protein loss occurs in a hypertrophic cardiomyopathy human heart with a pathogenic MYH7 variant. We then differentiated the MYH7 missense variant hiPSC library to cardiomyocytes for multiplexed assessment of ß-MHC variant abundance by massively parallel sequencing and hiPSC-derived cardiomyocyte survival. RESULTS: Both the multiplexed assessment of ß-MHC abundance and hiPSC-derived cardiomyocyte survival accurately segregated all known pathogenic variants from synonymous variants. Functional data were generated for 4 variants of unknown significance and 58 additional MYH7 missense variants not yet detected in patients. CONCLUSIONS: This study leveraged hiPSC differentiation into disease-relevant cardiomyocytes to enable multiplexed assessments of MYH7 missense variants for the first time. Phenotyping strategies used here enable the application of deep mutational scanning to clinically actionable genes, which should reduce the burden of variants of unknown significance on patients and clinicians.

Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD.

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD ('ocGVHD'), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Of 92 patients who developed cGVHD, 35 were classified as ocGVHD. The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX+placebo and CNI/MTX+abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. OcGVHD is associated with increased cGVHD severity scores, and is associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype.

A novel in vivo system to study coral biomineralization in the starlet sea anemone, Nematostella vectensis.

Coral conservation requires a mechanistic understanding of how environmental stresses disrupt biomineralization, but progress has been slow, primarily because corals are not easily amenable to laboratory research. Here, we highlight how the starlet sea anemone, Nematostella vectensis, can serve as a model to interrogate the cellular mechanisms of coral biomineralization. We have developed transgenic constructs using biomineralizing genes that can be injected into Nematostella zygotes and designed such that translated proteins may be purified for physicochemical characterization. Using fluorescent tags, we confirm the ectopic expression of the coral biomineralizing protein, SpCARP1, in Nematostella. We demonstrate via calcein staining that SpCARP1 concentrates calcium ions in Nematostella, likely initiating the formation of mineral precursors, consistent with its suspected role in corals. These results lay a fundamental groundwork for establishing Nematostella as an in vivo system to explore the evolutionary and cellular mechanisms of coral biomineralization, improve coral conservation efforts, and even develop novel biomaterials.