Assessing Patient-Reported Experiences for In-Person and Telemedicine-Based Preoperative Evaluations.

Background: The COVID-19 pandemic has transformed health care delivery through the rise of telehealth solutions. Though telemedicine-based care has been identified as safe and feasible in postoperative care, data on initial surgical consultations in the preoperative setting are lacking. We sought to compare patient characteristics, anticipated downstream care utilization, and patient-reported experiences (PREs) for in-person versus telemedicine-based care conducted for initial consultation encounters at a hernia and abdominal wall center. Methods: Patients evaluated at an abdominal wall reconstruction center from August 2021 to August 2022 were prospectively surveyed. Patient characteristics, anticipated downstream care utilization, and PREs were compared. Results: Of the 176 respondents, 50.6% (n = 89) utilized telemedicine-based care and had similar demographic and disease characteristics to those receiving in-person care. Telemedicine-based care saved a median of 47 min [interquartile range 20-112.5 min] of round-trip travel time per patient, with 10.1% of encounters resulting in supplemental in-person evaluation. A large proportion of telemedicine-based and in-person encounters resulted in recommendations for operative intervention, 38.2% versus 55.2%, respectively. Indirect costs of care were significantly lower for patients utilizing telemedicine-based services. Patient satisfaction related to encounters was non-inferior to in-person care. Overall, the majority of patients responded that they preferred future care to be delivered via telemedicine-based services, if offered. Conclusions: Preoperative telemedicine-based care was associated with significant cost-savings over in-person care related with comparable patient satisfaction. Health systems should continue to dedicate resources to optimizing and expanding perioperative telemedicine capabilities.

Understanding Post-Esophagectomy Complications and Their Management: The Early Complications.

Esophagectomy is a technically complex operation performed for both benign and malignant esophageal disease. Medical and surgical advancements have led to improved outcomes in esophagectomy patients over the past several decades; however, surgeons must remain vigilant as complications happen often and can be severe. Post-esophagectomy complications can be grouped into early and late categories. The aim of this review is to discuss the early complications of esophagectomy along with their risk factors, work-up, and management strategies with special attention given to anastomotic leaks.

Retrospective Analysis of Wastewater-Based Epidemiology of SARS-CoV-2 in Residences on a Large College Campus: Relationships between Wastewater Outcomes and COVID-19 Cases across Two Semesters with Different COVID-19 Mitigation Policies.

Wastewater-based epidemiology (WBE) has been utilized for outbreak monitoring and response efforts in university settings during the coronavirus disease 2019 (COVID-19) pandemic. However, few studies examined the impact of university policies on the effectiveness of WBE to identify cases and mitigate transmission. The objective of this study was to retrospectively assess relationships between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wastewater outcomes and COVID-19 cases in residential buildings of a large university campus across two academic semesters (August 2020-May 2021) under different COVID-19 mitigation policies. Clinical case surveillance data of student residents were obtained from the university COVID-19 response program. We collected and processed building-level wastewater for detection and quantification of SARS-CoV-2 RNA by RT-qPCR. The odds of obtaining a positive wastewater sample increased with COVID-19 clinical cases in the fall semester (OR = 1.50, P value = 0.02), with higher odds in the spring semester (OR = 2.63, P value < 0.0001). We observed linear associations between SARS-CoV-2 wastewater concentrations and COVID-19 clinical cases (parameter estimate = 1.2, P value = 0.006). Our study demonstrated the effectiveness of WBE in the university setting, though it may be limited under different COVID-19 mitigation policies. As a complementary surveillance tool, WBE should be accompanied by robust administrative and clinical testing efforts for the COVID-19 pandemic response.

Gut microbial metabolites and its impact on human health.

One of the primary methods by which the gut microbiome interacts with its host is through the interactions that occur through the production of the metabolites produced, either directly, or indirectly, through microbial metabolism. Decades of research has demonstrated that these metabolic products play a vital role in human health, either for its benefit or detriment. This review article highlights the main metabolites produced by the interactions between diet and the gut microbiome, bile acids and the gut microbiome, and products produced by the gut microbiome alone. Additionally, this article reviews the literature on the effects that these metabolites play on human health.

Traffic noise inhibits inhibitory control in wild-caught songbirds.

Anthropogenic noise is ubiquitous across environments and can have negative effects on animals, ranging from physiology to community structure. Recent work with captive-bred zebra finches demonstrated that traffic noise also affects cognitive performance. We examined whether these results extend to animals that have experienced noise in the wild. We collected black-capped chickadees from areas frequently exposed to road traffic noise and tested them on a detour reaching task, a commonly used measure of inhibitory control. Those chickadees exposed to traffic noise playback had much lower performance on the task than control birds, indicating that noise negatively impacts inhibitory control. These data corroborate previous findings in lab-reared zebra finches. Furthermore, these results suggest that prior experience with traffic noise is not sufficient for animals to habituate to noise and overcome its negative effects on cognitive performance. Instead, noise-induced cognitive effects might have broad impacts on animal species living in noise-polluted habitats.

Impact of Morbid Obesity on Post-esophagectomy Leak Rate: a NSQIP Analysis.

BACKGROUND: Morbid obesity is becoming more prevalent and is a known risk factor for esophageal cancer. Esophagectomy in this population is technically more challenging than the non-obese, thus increasing the risks of surgery. This study hypothesizes that higher body mass index (BMI) is associated with higher anastomotic leak rates after esophagectomy. METHODS: This study is a retrospective review of patients undergoing esophagectomy in the National Surgical Quality Improvement Program (NSQIP) Targeted Esophagectomy database from 2016 to 2019. Patients were stratified by BMI < 35 versus BMI > 35, with the primary outcome being leak post-esophagectomy. Univariate analyses were performed for demographics and post-operative outcomes, and multivariate analyses were performed specifically for the primary outcome of anastomotic leak (all diagnoses and malignancy/dysplasia subgroup). This study was approved by the Institutional Review Board. RESULTS: Of 4165 patients, 439 (10.5%) had a BMI > 35. Patients with BMI > 35 were often younger (mean age 60 vs 64 years, p < 0.001), White (p < 0.001), female (p < 0.001), non-smoker (p < 0.001), diabetic (p < 0.001), with hypertension (p < 0.001), and ASA ≥ 3 (p < 0.001). There were no differences between BMI groups with regard to indication for esophagectomy (malignancy/dysphasia vs other), conversion to open, mortality, or length of stay. The BMI > 35 cohort reported higher operative times (p < 0.001), open operative approach (p = 0.04), superficial surgical site infection (p < 0.001), return to operating room (p = 0.01), and leak (13.5% vs 10.1%, p = 0.01). BMI > 35 was not an independent predictor of leak for all diagnoses; however, the subgroup analysis of esophagectomy for malignancy/dysplasia demonstrated that BMI > 35 was predictive of leak (OR 1.42, 95% CI 1.05-1.91), as well as operative time and hypertension. CONCLUSION: Patients with a BMI > 35 and who undergo esophagectomy have a higher rate of anastomotic leak. BMI > 35 was also an independent predictor of leak when esophagectomy was performed for malignancy/dysplasia, but not for all diagnoses. The risk of anastomotic leak should be considered in morbidly obese patients undergoing esophagectomy, particularly for malignancy.

Bedside vs webside: Assessing patient-reported experiences for in-person and telemedicine-based perioperative evaluations.

BACKGROUND: Though telemedicine has been identified as safe and feasible, data on patient reported experiences (PREs) are lacking. We sought to compare PREs between in-person and telemedicine-based perioperative care. METHODS: Patients evaluated from August-November 2021 were prospectively surveyed to assess experiences and satisfaction with care rendered during in-person and telemedicine-based encounters. Patient and hernia characteristics, encounter related plans, and PREs were compared between in-person and telemedicine-based care. RESULTS: Of 109 respondents (86% response rate), 55% (n = 60) utilized telemedicine-based perioperative care. Indirect costs were lower for patients using telemedicine-based services, including work absence (3% vs. 33%, P < 0.001), lost wages (0% vs. 14%, P = 0.003), and requirements for hotel accommodations (0% vs. 12%, P = 0.007). PREs related to telemedicine-based care were non-inferior to in-person care across all measured domains (P > 0.4). CONCLUSIONS: Telemedicine-based care yields significant cost-savings over in-person care with similar patient satisfaction. These findings suggest that systems should focus on optimization of perioperative telemedicine services.

A transgenic Alx4-CreER mouse to analyze anterior limb and nephric duct development.

BACKGROUND: Genetic tools to study gene function and the fate of cells in the anterior limb bud are very limited. RESULTS: We describe a transgenic mouse line expressing CreERT2 from the Aristaless-like 4 (Alx4) promoter that induces recombination in the anterior limb. Cre induction at embryonic day 8.5 revealed that Alx4-CreERT2 labeled cells using the mTmG Cre reporter contributed to anterior digits I to III as well as the radius of the forelimb. Cre activity is expanded further along the AP axis in the hindlimb than in the forelimb resulting in some Cre reporter cells contributing to digit IV. Induction at later time points labeled cells that become progressively restricted to more anterior digits and proximal structures. Comparison of Cre expression from the Alx4 promoter transgene with endogenous Alx4 expression reveals Cre expression is slightly expanded posteriorly relative to the endogenous Alx4 expression. Using Alx4-CreERT2 to induce loss of intraflagellar transport 88 (Ift88), a gene required for ciliogenesis, hedgehog signaling, and limb patterning, did not cause overt skeletal malformations. However, the efficiency of deletion, time needed for Ift88 protein turnover, and for cilia to regress may hinder using this approach to analyze cilia in the limb. Alx4-CreERT2 is also active in the mesonephros and nephric duct that contribute to the collecting tubules and ducts of the adult nephron. Embryonic activation of the Alx4-CreERT2 in the Ift88 conditional line results in cyst formation in the collecting tubules/ducts. CONCLUSION: Overall, the Alx4-CreERT2 line will be a new tool to assess cell fates and analyze gene function in the anterior limb, mesonephros, and nephric duct.

Transcription factor Ap2b regulates the mouse autosomal recessive polycystic kidney disease genes, Pkhd1 and Cys1.

Transcription factor Ap2b (TFAP2B), an AP-2 family transcription factor, binds to the palindromic consensus DNA sequence, 5'-GCCN3-5GGC-3'. Mice lacking functional Tfap2b gene die in the perinatal or neonatal period with cystic dilatation of the kidney distal tubules and collecting ducts, a phenotype resembling autosomal recessive polycystic kidney disease (ARPKD). Human ARPKD is caused by mutations in PKHD1, DZIP1L, and CYS1, which are conserved in mammals. In this study, we examined the potential role of TFAP2B as a common regulator of Pkhd1 and Cys1. We determined the transcription start site (TSS) of Cys1 using 5' Rapid Amplification of cDNA Ends (5'RACE); the TSS of Pkhd1 has been previously established. Bioinformatic approaches identified cis-regulatory elements, including two TFAP2B consensus binding sites, in the upstream regulatory regions of both Pkhd1 and Cys1. Based on reporter gene assays performed in mouse renal collecting duct cells (mIMCD-3), TFAP2B activated the Pkhd1 and Cys1 promoters and electromobility shift assay (EMSA) confirmed TFAP2B binding to the in silico identified sites. These results suggest that Tfap2b participates in a renal epithelial cell gene regulatory network that includes Pkhd1 and Cys1. Disruption of this network impairs renal tubular differentiation, causing ductal dilatation that is the hallmark of recessive PKD.

Pyoderma Gangrenosum: A Literature Review.

Pyoderma gangrenosum (PG), which most frequently affects the lower extremity, is a complicated disease state that results from a combination of inflammation, neutrophilic invasion, and genetic predisposition. There may also be certain comorbidities involved or it may be idiopathic. The many variations of PG mean that it often presents and responds differently to various treatments based on the specific case. Overall, there have been improvements in understanding the disease; however, further research should focus on finding better ways to predict and prevent this rapidly progressive, painful disease.

Cystin genetic variants cause autosomal recessive polycystic kidney disease associated with altered Myc expression.

Mutation of the Cys1 gene underlies the renal cystic disease in the Cys1cpk/cpk (cpk) mouse that phenocopies human autosomal recessive polycystic kidney disease (ARPKD). Cystin, the protein product of Cys1, is expressed in the primary apical cilia of renal ductal epithelial cells. In previous studies, we showed that cystin regulates Myc expression via interaction with the tumor suppressor, necdin. Here, we demonstrate rescue of the cpk renal phenotype by kidney-specific expression of a cystin-GFP fusion protein encoded by a transgene integrated into the Rosa26 locus. In addition, we show that expression of the cystin-GFP fusion protein in collecting duct cells down-regulates expression of Myc in cpk kidneys. Finally, we report the first human patient with an ARPKD phenotype due to homozygosity for a deleterious splicing variant in CYS1. These findings suggest that mutations in Cys1/CYS1 cause an ARPKD phenotype in mouse and human, respectively, and that the renal cystic phenotype in the mouse is driven by overexpression of the Myc proto-oncogene.

The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype.

The glycosyltransferase ST6Gal-I, which adds α2-6-linked sialic acids to substrate glycoproteins, has been implicated in carcinogenesis; however, the nature of its pathogenic role remains poorly understood. Here we show that ST6Gal-I is upregulated in ovarian and pancreatic carcinomas, enriched in metastatic tumors, and associated with reduced patient survival. Notably, ST6Gal-I upregulation in cancer cells conferred hallmark cancer stem-like cell (CSC) characteristics. Modulating ST6Gal-I expression in pancreatic and ovarian cancer cells directly altered CSC spheroid growth, and clonal variants with high ST6Gal-I activity preferentially survived in CSC culture. Primary ovarian cancer cells from patient ascites or solid tumors sorted for α2-6 sialylation grew as spheroids, while cells lacking α2-6 sialylation remained as single cells and lost viability. ST6Gal-I also promoted resistance to gemcitabine and enabled the formation of stably resistant colonies. Gemcitabine treatment of patient-derived xenograft tumors enriched for ST6Gal-I-expressing cells relative to pair-matched untreated tumors. ST6Gal-I also augmented tumor-initiating potential. In limiting dilution assays, subcutaneous tumor formation was inhibited by ST6Gal-I knockdown, whereas in a chemically induced tumor initiation model, mice with conditional ST6Gal-I overexpression exhibited enhanced tumorigenesis. Finally, we found that ST6Gal-I induced expression of the key tumor-promoting transcription factors, Sox9 and Slug. Collectively, this work highlighted a previously unrecognized role for a specific glycosyltransferase in driving a CSC state. Cancer Res; 76(13); 3978-88. ©2016 AACR.

Magnetic resonance microscopy of renal and biliary abnormalities in excised tissues from a mouse model of autosomal recessive polycystic kidney disease.

Polycystic kidney disease (PKD) is transmitted as either an autosomal dominant or recessive trait and is a major cause of renal failure and liver fibrosis. The cpk mouse model of autosomal recessive PKD (ARPKD) has been extensively characterized using standard histopathological techniques after euthanasia. In the current study, we sought to validate magnetic resonance microscopy (MRM) as a robust tool for assessing the ARPKD phenotype. We used MRM to evaluate the liver and kidney of wild-type and cpk animals at resolutions <100 µm and generated three-dimensional (3D) renderings for pathological evaluation. Our study demonstrates that MRM is an excellent method for evaluating the complex, 3D structural defects in this ARPKD mouse model. We found that MRM was equivalent to water displacement in assessing kidney volume. Additionally, using MRM we demonstrated for the first time that the cpk liver exhibits less extensive ductal arborization, that it was reduced in volume, and that the ductal volume was disproportionately smaller. Histopathology indicates that this is a consequence of bile duct malformation. With its reduced processing time, volumetric information, and 3D capabilities, MRM will be a useful tool for future in vivo and longitudinal studies of disease progression in ARPKD. In addition, MRM will provide a unique tool to determine whether the human disease shares the newly appreciated features of the murine biliary phenotype.

Intragenic motifs regulate the transcriptional complexity of Pkhd1/PKHD1.

Autosomal recessive polycystic kidney disease (ARPKD) results from mutations in the human PKHD1 gene. Both this gene, and its mouse ortholog, Pkhd1, are primarily expressed in renal and biliary ductal structures. The mouse protein product, fibrocystin/polyductin complex (FPC), is a 445-kDa protein encoded by a 67-exon transcript that spans >500 kb of genomic DNA. In the current study, we observed multiple alternatively spliced Pkhd1 transcripts that varied in size and exon composition in embryonic mouse kidney, liver, and placenta samples, as well as among adult mouse pancreas, brain, heart, lung, testes, liver, and kidney. Using reverse transcription PCR and RNASeq, we identified 22 novel Pkhd1 kidney transcripts with unique exon junctions. Various mechanisms of alternative splicing were observed, including exon skipping, use of alternate acceptor/donor splice sites, and inclusion of novel exons. Bioinformatic analyses identified, and exon-trapping minigene experiments validated, consensus binding sites for serine/arginine-rich proteins that modulate alternative splicing. Using site-directed mutagenesis, we examined the functional importance of selected splice enhancers. In addition, we demonstrated that many of the novel transcripts were polysome bound, thus likely translated. Finally, we determined that the human PKHD1 R760H missense variant alters a splice enhancer motif that disrupts exon splicing in vitro and is predicted to truncate the protein. Taken together, these data provide evidence of the complex transcriptional regulation of Pkhd1/PKHD1 and identified motifs that regulate its splicing. Our studies indicate that Pkhd1/PKHD1 transcription is modulated, in part by intragenic factors, suggesting that aberrant PKHD1 splicing represents an unappreciated pathogenic mechanism in ARPKD. Key messages: Multiple mRNA transcripts are generated for Pkhd1 in renal tissues Pkhd1 transcription is modulated by standard splice elements and effectors Mutations in splice motifs may alter splicing to generate nonfunctional peptides.

An inducible CiliaGFP mouse model for in vivo visualization and analysis of cilia in live tissue.

BACKGROUND: Cilia are found on nearly every cell type in the mammalian body, and have been historically classified as either motile or immotile. Motile cilia are important for fluid and cellular movement; however, the roles of non-motile or primary cilia in most tissues remain unknown. Several genetic syndromes, called the ciliopathies, are associated with defects in cilia structure or function and have a wide range of clinical presentations. Much of what we know about the formation and maintenance of cilia comes from model systems like C. elegans and Chalmydomonas. Studies of mammalian cilia in live tissues have been hampered by difficulty visualizing them. RESULTS: To facilitate analyses of mammalian cilia function we generated an inducible CiliaGFP mouse by targeting mouse cDNA encoding a cilia-localized protein somatostatin receptor 3 fused to GFP (Sstr3::GFP) into the ROSA26 locus. In this system, Sstr3::GFP is expressed from the ubiquitous ROSA26 promoter after Cre mediated deletion of an upstream Neo cassette flanked by lox P sites. Fluorescent cilia labeling was observed in a variety of live tissues and after fixation. Both cell-type specific and temporally regulated cilia labeling were obtained using multiple Cre lines. The analysis of renal cilia in anesthetized live mice demonstrates that cilia commonly lay nearly parallel to the apical surface of the tubule. In contrast, in more deeply anesthetized mice the cilia display a synchronized, repetitive oscillation that ceases upon death, suggesting a relationship to heart beat, blood pressure or glomerular filtration. CONCLUSIONS: The ability to visualize cilia in live samples within the CiliaGFP mouse will greatly aid studies of ciliary function. This mouse will be useful for in vivo genetic and pharmacological screens to assess pathways regulating cilia motility, signaling, assembly, trafficking, resorption and length control and to study cilia regulated physiology in relation to ciliopathy phenotypes.

Proximal tubule proliferation is insufficient to induce rapid cyst formation after cilia disruption.

Disrupting the function of cilia in mouse kidneys results in rapid or slow progression of cystic disease depending on whether the animals are juveniles or adults, respectively. Renal injury can also markedly accelerate the renal cyst formation that occurs after disruption of cilia in adult mice. Rates of cell proliferation are markedly higher in juvenile than adult kidneys and increase after renal injury, suggesting that cell proliferation may enhance the development of cysts. Here, we induced cilia loss in the kidneys of adult mice in the presence or absence of a Cux-1 transgene, which maintains cell proliferation. By using this model, we were able to avoid additional factors such as inflammation and dedifferentiation, which associate with renal injury and may also influence the rate of cystogenesis. After induction of cilia loss, cystic disease was not more pronounced in adult mice with the Cux-1 transgene compared with those without the transgene. In conclusion, these data suggest that proliferation is unlikely to be the sole mechanism underlying the rapid cystogenesis observed after injury in mice that lose cilia function in adulthood.

Role of epidermal primary cilia in the homeostasis of skin and hair follicles.

Skin and hair follicle morphogenesis and homeostasis require the integration of multiple signaling pathways, including Hedgehog (Hh) and Wingless (Wnt), and oriented cell divisions, all of which have been associated with primary cilia. Although studies have shown that disrupting dermal cilia causes follicular arrest and attenuated Hh signaling, little is known about the role of epidermal cilia. Here, epidermal cilia function was analyzed using conditional alleles of the ciliogenic genes Ift88 and Kif3a. At birth, epidermal cilia mutants appeared normal, but developed basaloid hyperplasia and ingrowths into the dermis of the ventrum with age. In addition, follicles in the tail were disorganized and had excess sebaceous gland lobules. Epidermal cilia mutants displayed fewer long-term label-retaining cells, suggesting altered stem cell homeostasis. Abnormal proliferation and differentiation were evident from lineage-tracing studies and showed an expansion of follicular cells into the interfollicular epidermis, as is seen during wound repair. These phenotypes were not associated with changes in canonical Wnt activity or oriented cell division. However, nuclear accumulation of the ΔNp63 transcription factor, which is involved in stratification, keratinocyte differentiation and wound repair, was increased, whereas the Hh pathway was repressed. Intriguingly, the phenotypes were not typical of those associated with loss of Hh signaling but exhibited similarities with those of mice in which ΔNp63 is overexpressed in the epidermis. Collectively, these data indicate that epidermal primary cilia may function in stress responses and epidermal homeostasis involving pathways other than those typically associated with primary cilia.

The primary cilium as a complex signaling center.

Respect for the primary cilium has undergone a remarkable renaissance over the past decade, and it is now thought to be an essential regulator of numerous signaling pathways. The primary cilium's functions range from the movement of cells and fluid, to sensory inputs involved with olfaction and photoreception. Disruption of cilia function is involved in multiple human syndromes collectively called 'ciliopathies'. The cilium's activities are mediated by targeting of receptors, channels, and their downstream effector proteins to the ciliary or basal body compartment. These combined properties of the cilium make it a critical organelle facilitating the interactions between the cell and its environment. Here, we review many of the recent advances contributing to the ascendancy of the primary cilium and how the extraordinary complexity of this organelle inevitably assures many more exciting future discoveries.

Generating conditional mutants to analyze ciliary functions: the use of Cre-lox technology to disrupt cilia in specific organs.

The list of human disordered associated with cilia dysfunction, the ciliopathies, continues to highlight the importance of understanding the many roles of the long overlooked primary cilium. Much of the insights into the clinical importance of the cilium have come from analyses in model organisms, especially the mouse. However, the early embryonic lethality and severe developmental defects associated with cilia disruption has hindered progress in exploring cilia functions in late development or in adult tissues. This hurdle is being surmounted through the use of conditional alleles of genes encoding ciliary proteins and Cre deletor lines with inducible Cre activity or with lines expressing Cre in a cell-type-specific manner. Results from these approaches are providing important insights into the diverse array of cellular and tissue activities regulated by the cilium. Here we provide a recent account of the Cre/lox strategy. The generation and use of well-designed conditional alleles, as well as careful manipulation of embryonic stem cells are discussed. We also provide specific examples to illustrate the use of Cre/lox approaches to evaluate ciliary function in several tissues. With the recent characterization of multiple cilia proteomes along with efforts of several consortia to generate conditional alleles of all genes in the mouse, further use of conditional mutation approaches promise to yield many advances and surprises as we explore the functions of this increasingly complex organelle.

Depletion of beta-COP reveals a role for COP-I in compartmentalization of secretory compartments and in biosynthetic transport of caveolin-1.

We have utilized small interfering RNA (siRNA)-mediated depletion of the beta-COP subunit of COP-I to explore COP-I function in organellar compartmentalization and protein traffic. Reduction in beta-COP levels causes the colocalization of markers for the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), Golgi, trans-Golgi network (TGN), and recycling endosomes in large, globular compartments. The lack of spatial differentiation of these compartments is not due to a general collapse of all cellular organelles since markers for the early endosomes and lysosomes do not redistribute to the common structures. Anterograde trafficking of the transmembrane cargo vesicular stomatitis virus membrane glycoprotein and of a subset of soluble cargoes is arrested within the common globular compartments. Similarly, recycling traffic of transferrin through the common compartment is perturbed. Furthermore, the trafficking of caveolin-1 (Cav1), a structural protein of caveolae, is arrested within the globular structures. Importantly, Cav1 coprecipitates with the gamma-subunit of COP-I, suggesting that Cav1 is a COP-I cargo. Our findings suggest that COP-I is required for the compartmentalization of the ERGIC, Golgi, TGN, and recycling endosomes and that COP-I plays a novel role in the biosynthetic transport of Cav1.