Clinical outcomes and mortality in patients with atrial fibrillation and recently diagnosed lung cancer in oncology outpatient settings.

INTRODUCTION: Our aim was to investigate the prevalence of atrial fibrillation (AF) and recently diagnosed lung cancer in the outpatient oncology clinic and to describe the clinical profile, management and outcomes of this population. METHODS: Among 6984 patients visited at the outpatient oncology clinics attending lung cancer patients in five university hospitals from 2017 to 2019, all consecutive subjects with recently diagnosed (<1 year) disease and AF were retrospectively selected and events in follow up were registered. RESULTS: A total of 269 patients (3.9 % of all attended, 71 ± 8 years, 91 % male) were included. Charlson, CHA2DS2-VASc and HAS-BLED indexes were 6.7 ± 2.9, 2.9 ± 1.5 y 2.5 ± 1.2, respectively. Tumour stage was I, II, III and IV in 11 %, 11 %, 33 % and 45 % of them, respectively. Anticoagulants were prescribed to 226 patients (84 %): direct anticoagulants (n = 99;44 %), low molecular weight heparins (n = 69;30 %) and vitamin K antagonists (n = 58;26 %). After 46 months of maximum follow-up, 186 patients died (69 %). Cumulative incidences of events at 3 years were 3.3 ± 1.3 % for stroke/systemic embolism (n = 7); 8.9 ± 2.2 % for thrombotic events (n = 18); 9.9 ± 2.6 % for major bleeding (n = 16), and 15.9 ± 3,0 % for cardiovascular events (n = 33). In patients with early stages of cancer (I-II), 2-year mortality was significantly higher in those with cardiovascular events or major bleeding (85 % vs 25 %, p = 0.01). CONCLUSION: Nearly 4 % or all outpatients in the oncology clinic attending lung cancer present recently diagnosed disease and AF. Major bleeding and cardiovascular event rates are high in this population, with an impact on mortality in early stages of cancer.

Antiproliferative effect of natural and semisynthetic polyethers from Laurencia viridis.

Squalene-derived polyethers are a unique class of compounds that display a great diversity of structures and a broad array of bioactivities, among which its notable antiproliferative activity stands out against various types of cancer cell lines. In this study, eighteen triterpene squalene-derived polyethers, including twelve natural products and six synthetic derivatives, obtained from the red alga Laurencia viridis Gil-Rodríguez & Haroun were screened for their antiproliferative activity against six cancer cell lines: A549, HBL-100, HeLa, SW1573, T-47D, and WiDr; and a structure-activity relationship (SAR) study was established.

Marine Meroterpenoids Isolated from Gongolaria abies-marina Induce Programmed Cell Death in Naegleria fowleri.

Naegleria fowleri is the causative agent of a central nervous system affecting disease called primary amoebic meningoencephalitis. It is a fulminant disease with a rapid progression that affects mainly children and young adults who report previous water exposure. Current treatment options are not totally effective and involve several side effects. In this work, six meroterpenoids isolated from the brown algae Gongolaria abies-marina were evaluated against N. fowleri. Gongolarone B (1), 6Z-1'-methoxyamentadione (2), and 1'-methoxyamentadione (3) were the most active molecules against N. fowleri with IC50 values between 13.27 ± 0.96 µM and 21.92 ± 1.60 µM. However, cystomexicone B (6) was the molecule with the highest selectivity index (>8.5). Moreover, all these compounds induced different cellular events compatible with the apoptosis-like PCD process, such as chromatin condensation, damages at the mitochondrial level, cell membrane disruption, and production of reactive oxygen species (ROS). Therefore, G. abies-marina could be considered as a promising source of active molecules to treat the N. fowleri infections.

Chamigrane-Type Sesquiterpenes from Laurencia dendroidea as Lead Compounds against Naegleria fowleri.

Naegleria fowleri is an opportunistic protozoon that can be found in warm water bodies. It is the causative agent of the primary amoebic meningoencephalitis. Focused on our interest to develop promising lead structures for the development of antiparasitic agents, this study was aimed at identifying new anti-Naegleria marine natural products from a collection of chamigrane-type sesquiterpenes with structural variety in the levels of saturation, halogenation and oxygenation isolated from Laurencia dendroidea. (+)-Elatol (1) was the most active compound against Naegleria fowleri trophozoites with IC50 values of 1.08 µM against the ATCC 30808™ strain and 1.14 µM against the ATCC 30215™ strain. Furthermore, the activity of (+)-elatol (1) against the resistant stage of N. fowleri was also assessed, showing great cysticidal properties with a very similar IC50 value (1.14 µM) to the one obtained for the trophozoite stage. Moreover, at low concentrations (+)-elatol (1) showed no toxic effect towards murine macrophages and could induce the appearance of different cellular events related to the programmed cell death, such as an increase of the plasma membrane permeability, reactive oxygen species overproduction, mitochondrial malfunction or chromatin condensation. Its enantiomer (-)-elatol (2) was shown to be 34-fold less potent with an IC50 of 36.77 µM and 38.03 µM. An analysis of the structure-activity relationship suggests that dehalogenation leads to a significant decrease of activity. The lipophilic character of these compounds is an essential property to cross the blood-brain barrier, therefore they represent interesting chemical scaffolds to develop new drugs.

Gongolarones as antiamoeboid chemical scaffold.

Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe eye infection known as Acanthamoeba keratitis (AK). Current studies focused on therapy against these diseases are aiming to find novel compounds with amoebicidal activity and low toxicity to human tissues. Brown algae, such as Gongolaria abies-marina (previously known as Cystoseira abies-marina, S.G. Gmelin), presents bioactive molecules of interest, including some with antiprotozoal activity. In this study, six meroterpenoids were isolated and purified from the species Gongolaria abies-marina. Gongolarones A (1), B (2) and C (3) were identified as new compounds. Additionally, cystomexicone B (4), 1'-methoxyamentadione (5) and 6Z-1'-methoxyamentadione (6) were isolated. All compounds exhibited amoebicidal activity against Acanthamoeba castellanii Neff, A. polyphaga and A. griffini strains. Gongolarones A (1) and C (3) showed the lowest IC50 values against the two stages of these amoebae (trophozoite and cyst). Structure-activity relationship revealed that the cyclization by ether formation from C-12 to C-15 of 1, and the isomerization Δ2 t to Δ3 t of 3, increased the antiamoeboid activity of both compounds. Furthermore, gongolarones A (1) and C (3) triggered chromatin condensation, mitochondrial malfunction, oxidative stress, and disorganization of the tubulin-actin cytoskeleton in treated trophozoites. Moreover, transmission electron microscopy (TEM) images analysis revealed that compounds 1 and 3 induced autophagy process and inhibited the encystation process. All those results suggest that both compounds could induce programmed cell death (PCD) in Acanthamoeba.

Squamins C-F, four cyclopeptides from the seeds of Annona globiflora.

Four cyclic octapeptides, squamins C-F, were isolated from the seeds of Annona globiflora Schltdl. These compounds share part of their amino acid sequence, -Pro-Met(O)-Tyr-Gly-Thr-, with previously reported squamins A and B. Their structures were determined using NMR spectroscopic techniques together with quantum mechanical calculations (QM-NMR), ESI-HRMS data and a modified version of Marfey's chromatographic method. All compounds showed cytotoxic activity against DU-145 (human prostate cancer) and HeLa (human cervical carcinoma) cell lines. Clearly, A. globiflora is an important source of bioactive molecules, which could promote the sustainable exploitation of this undervalued specie.

Antiamoeboid activity of squamins C-F, cyclooctapeptides from Annona globifora.

Free-living amoebae of Acanthamoeba spp. are causative agents of human infections such as granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The exploration of innovative chemical entities from natural sources that induce intrinsic apoptotic pathway or a Programmed Cell Death (PCD) in Acanthamoeba protozoa is essential to develop new therapeutic strategies. In this work, the antiamoeboid activity of squamins C-F (1-4), four cyclooctapeptides isolated from Annona globiflora was tested in vitro against Acanthamoeba castellanii Neff, A. polyphaga, A. quina, and A. griffini, and a structure-activity relationship was also established. The most sensitive strain against all tested cyclooctapeptides was A. castellanii Neff being the R conformers of the S-oxo-methionine residue, squamins D (2) and F (4), the most active against the trophozoite stage. It is remarkable that all four peptides showed no cytotoxic effects against murine macrophages cell line J774A.1. The analysis of the mode of action of squamins C-F against A. castellanii indicate that these cyclopeptides induced the mechanisms of programmed cell death (PCD). All peptides trigger mitochondrial damages, significant inhibition of ATP production compared to the negative control, chromatin condensation and slight damages in membrane that affects its permeability despite it conserves integrity at the IC90 for 24 h. An increase in reactive oxygen species (ROS) was observed in all cases.

Antiamoebic effects of sesquiterpene lactones isolated from the zoanthid Palythoa aff. clavata.

Opportunistic parasitic protozoa of genus Acanthamoeba are responsible to cause severe infections in humans such as Acanthamoeba Keratitis or Amoebic Granulomatous Encephalitis. Current treatments are usually toxic and inefficient and there is a need to access new therapeutic agents. The antiamoebic effects of nephthediol (1) and fourteen germacranolide and eudesmanolide sesquiterpene lactones (2-5, 7-12) isolated from the indigenous zoanthid Palythoa aff. clavata collected at the coast of Lanzarote, Canary Islands were studied against Acanthamoeba castellanii Neff, and the clinical strains A. polyphaga and A. griffini. 4-epi-arbusculin A (11) presented the lowest IC50 value (26,47 ± 1,69 µM) against A. castellanii Neff and low cytotoxicity against murine macrophages, followed by isobadgerin (2), which also showed to be active against A. castellanii Neff cysts. The studies on the mode of action of compounds 2 and 11 revealed these sesquiterpene lactones induce mechanisms of PDC on A. castellanii Neff.

Antiproliferative potential of 3ß,5α,6ß,7α-tetrahydroxyergosta-8(14),22-diene produced by Acremonium persicinum isolated from an alkaline crater lake in Puebla, Mexico.

The sterol 3ß,5α,6ß,7α-tetrahydroxyergosta-8(14),22-diene was obtained from bio-guided fractioning of the chloroform extract of 50 L of liquid culture of Acremonium persicinum. This fungal strain was selected because of its anti-proliferative activity against solid human tumour cell lines (GI50 ≤ 50 µg/mL) in a bio-prospective study of fungi isolated from plant material, sediment and water samples obtained from alkaline lakes Alchichica and Atexcac in Puebla, Mexico. This compound showed GI50 (µM) values of: 16, 24, 18, 15 and 12 against tumour cell lines A-549, HBL-100, HeLa, T-47D and WiDr respectively. GI50 effects against tumour lines T-47D and WiDr were found to be greater than the clinically used drugs Etoposide and Cisplatin. Because of this, the results obtained support the pharmacological importance of the microorganisms that develop in these ecosystems and strengthen the non-invasive bio-prospection studies that our work group has developed in recent years.

Laurinterol from Laurencia johnstonii eliminates Naegleria fowleri triggering PCD by inhibition of ATPases.

Primary amoebic encephalitis (PAM) is a lethal disease caused by the opportunistic pathogen, Naegleria fowleri. This amoebic species is able to live freely in warm aquatic habitats and to infect children and young adults when they perform risk activities in these water bodies such as swimming or splashing. Besides the need to increase awareness of PAM which will allow an early diagnosis, the development of fully effective therapeutic agents is needed. Current treatment options are amphotericin B and miltefosine which are not fully effective and also present toxicity issues. In this study, the in vitro activity of various sesquiterpenes isolated from the red alga Laurencia johnstonii were tested against the trophozoite stage of a strain of Naegleria fowleri. Moreover, the induced effects (apoptotic cell death) of the most active compound, laurinterol (1), was evaluated by measuring DNA condensation, damages at the mitochondrial level, cell membrane disruption and production of reactive oxygen species (ROS). The obtained results demonstrated that laurinterol was able to eliminate the amoebae at concentrations of 13.42 ± 2.57 µM and also to induced programmed cell death (PCD) in the treated amoebae. Moreover, since ATP levels were highly affected and laurinterol has been previously reported as an inhibitor of the Na+/K+-ATPase sodium-potassium ion pump, comparison with known inhibitors of ATPases were carried out. Our results points out that laurinterol was able to inhibit ENA ATPase pump at concentrations 100 times lower than furosemide.

Polymorphisms in vasoactive eicosanoid genes of kidney donors affect biopsy scores and clinical outcomes in renal transplantation.

Cytochrome P450 (CYP) enzymes metabolize arachidonic acid to vasoactive eicosanoids such as epoxyeicosatrienoic acids (EETs) and 20-Hydroxyeicosatetraenoic acid (20-HETE), whilst soluble epoxide hydrolase, encoded by the EPHX2 gene, is in charge of EETs degradation. We aimed to analyze the influence of common, functional polymorphisms in four genes of the donor on the renal biopsy scores independently assigned by pathologists. Additionally, we examined whether this score or the presence of these SNPs were independent risk factors of clinical outcomes in the first year after grafting. A cohort of 119 recipients and their corresponding 85 deceased donors were included in the study. Donors were genotyped for the CYP4F2 V433M, CYP2C8*3, CYP2J2*7, EPHX2 3'UTR A>G, EPHX2 K55R and EPHX2 R287Q polymorphisms. The association of the donors' SNPs with the biopsy scores and clinical outcomes was retrospectively evaluated by multivariate regression analysis. The CYP2C8*3 polymorphism in the donor was significantly associated with higher scores assigned to pretransplant biopsies [OR = 3.35 (1.03-10.93), p = 0.045]. In turn, higher scores were related to an increased risk of acute rejection [OR = 5.28 (1.32-21.13), p = 0.019] and worse glomerular filtration rate (eGFR) (45.68±16.05 vs. 53.04±16.93 ml/min in patients whose grafts had lower scores, p = 0.010) one year after transplant. Patients whose donors carried the CYP4F2 433M variant showed lower eGFR values (48.96±16.89 vs. 55.94±18.62 ml/min in non-carriers, p = 0.038) and higher risk of acute rejection [OR = 6.18 (1.03-37.21), p = 0.047]. The CYP2J2*7 SNP in the donor was associated with elevated risk of delayed graft function [OR = 25.68 (1.52-43.53), p = 0.025]. Our results taken together suggest that donor genetic variability may be used as a predictor of tissue damage in the graft as well as to predict clinical outcomes and graft function in the recipient.

Evaluation of Oxasqualenoids from the Red Alga Laurencia viridis against Acanthamoeba.

Acanthamoeba genus is a widely distributed and opportunistic parasite with increasing importance worldwide as an emerging pathogen in the past decades. This protozoan has an active trophozoite stage, a cyst stage, and is dormant and very resistant. It can cause Acanthamoeba keratitis, an ocular sight-threatening disease, and granulomatous amoebic encephalitis, a chronic, very fatal brain pathology. In this study, the amoebicidal activity of sixteen Laurencia oxasqualenoid metabolites and semisynthetic derivatives were tested against Acanthamoeba castellanii Neff. The results obtained point out that iubol (3) and dehydrothyrsiferol (1) possess potent activities, with IC50 values of 5.30 and 12.83 µM, respectively. The hydroxylated congeners thyrsiferol (2) and 22-hydroxydehydrothyrsiferol (4), active in the same value range at IC50 13.97 and 17.00 µM, are not toxic against murine macrophages; thus, they are solid candidates for the development of new amoebicidal therapies.

Antiproliferative activity of biomass extract from Pseudomonas cedrina

Background: The study of plant-associated microorganisms is very important in the discovery and development of bioactive compounds. Pseudomonas is a diverse genus of Gammaproteobacteria comprising more than 60 species capable of establishing themselves in many habitats, which include leaves and stems of many plants. There are reports of metabolites with diverse biological activity obtained from bacteria of this genus, and some of the metabolites have shown cytotoxic activity against cancer cell lines. Because of the high incidence of cancer, research in recent years has focused on obtaining new sources of active compounds that exhibit interesting pharmacodynamic and pharmacokinetic properties that lead to the development of new therapeutic agents. Results: A bacterial strain was isolated from tumors located in the stem of Pinus patula, and it was identified as Pseudomonas cedrina. Extracts from biomass and broth of P. cedrina were obtained with chloroform:methanol (1:1). Only biomass extracts exhibited antiproliferative activity against human tumor cell lines of cervix (HeLa), lung (A-549), and breast (HBL-100). In addition, a biomass extract from P. cedrina was fractioned by silica gel column chromatography and two diketopiperazines were isolated: cyclo-(L-Prolyl-L-Valine) and cyclo-(L-Leucyl-L-Proline). Conclusions: This is the first report on the association of P. cedrina with the stems of P. patula in Mexico and the antiproliferative activity of extracts from this species of bacteria against human solid tumor cell lines.

Antitumoral Effect of Laurinterol on 3D Culture of Breast Cancer Explants.

Macroalgae represent an important source of bioactive compounds with a wide range of biotechnological applications. Overall, the discovery of effective cytotoxic compounds with pharmaceutical potential is a significant challenge, mostly because they are scarce in nature or their total synthesis is not efficient, while the bioprospecting models currently used do not predict clinical responses. Given this context, we used three-dimensional (3D) cultures of human breast cancer explants to evaluate the antitumoral effect of laurinterol, the major compound of an ethanolic extract of Laurencia johnstonii. To this end, we evaluated the metabolic and histopathological effects of the crude extract of L. johnstonii and laurinterol on Vero and MCF-7 cells, in addition to breast cancer explants. We observed a dose-dependent inhibition of the metabolic activity, as well as morphologic and nuclear changes characteristic of apoptosis. On the other hand, a reduced metabolic viability and marked necrosis areas were observed in breast cancer explants incubated with the crude extract, while explants treated with laurinterol exhibited a heterogeneous response which was associated with the individual response of each human tumor sample. This study supports the cytotoxic and antitumoral effects of laurinterol in in vitro cell cultures and in ex vivo organotypic cultures of human breast cancer explants.

Full Factorial Microfluidic Designs and Devices for Parallelizing Human Pluripotent Stem Cell Differentiation.

Human pluripotent stem cells (hPSCs) are promising therapeutic tools for regenerative therapies and disease modeling. Differentiation of cultured hPSCs is influenced by both exogenous factors added to the cultures and endogenously secreted molecules. Optimization of protocols for the differentiation of hPSCs into different cell types is difficult because of the many variables that can influence cell fate. We present microfluidic devices designed to perform three- and four-factor, two-level full factorial experiments in parallel for investigating and directly optimizing hPSC differentiation. These devices feature diffusion-isolated, independent culture wells that allow for control of both exogenous and endogenous cellular signals and that allow for immunocytochemistry (ICC) and confocal microscopy in situ. These devices are fabricated by soft lithography in conjunction with 3D-printed molds and are operable with a single syringe pump, eliminating the need for specialized equipment or cleanroom facilities. Their utility was demonstrated by on-chip differentiation of hPSCs into the auditory neuron lineage. More broadly, these devices enable multiplexing for experimentation with any adherent cell type or even multiple cell types, allowing efficient investigation of the effects of medium conditions, pharmaceuticals, or other soluble reagents.

The 9H-Fluoren Vinyl Ether Derivative SAM461 Inhibits Bacterial Luciferase Activity and Protects Artemia franciscana From Luminescent Vibriosis.

Vibrio campbellii is a major pathogen in aquaculture. It is a causative agent of the so-called "luminescent vibriosis," a life-threatening condition caused by bioluminescent Vibrio spp. that often involves mass mortality of farmed shrimps. The emergence of multidrug resistant Vibrio strains raises a concern and poses a challenge for the treatment of this infection in the coming years. Inhibition of bacterial cell-to-cell communication or quorum sensing (QS) has been proposed as an alternative to antibiotic therapies. Aiming to identify novel QS disruptors, the 9H-fluroen-9yl vinyl ether derivative SAM461 was found to thwart V. campbellii bioluminescence, a QS-regulated phenotype. Phenotypic and gene expression analyses revealed, however, that the mode of action of SAM461 was unrelated to QS inhibition. Further evaluation with purified Vibrio fischeri and NanoLuc luciferases revealed enzymatic inhibition at micromolar concentrations. In silico analysis by molecular docking suggested binding of SAM461 in the active site cavities of both luciferase enzymes. Subsequent in vivo testing of SAM461 with gnotobiotic Artemia franciscana nauplii demonstrated naupliar protection against V. campbellii infection at low micromolar concentrations. Taken together, these findings suggest that suppression of luciferase activity could constitute a novel paradigm in the development of alternative anti-infective chemotherapies against luminescent vibriosis, and pave the ground for the chemical synthesis and biological characterization of derivatives with promising antimicrobial prospects.

Antitumor activity of Lepidium latifolium and identification of the epithionitrile 1-cyano-2,3-epithiopropane as its major active component.

Consumption of Brassica (Cruciferae) vegetables is associated with a reduced risk of cancer, but identification of the active components and insights into the underlying molecular events are scarce. Here we found that an extract of Lepidium latifolium, a cruciferous plant native to southern Europe, Mediterranean countries and Asia, showed in vitro cytotoxic activity, inducing caspase-dependent apoptosis, in a variety of human tumor cells, and the plant juice showed in vivo antitumor activity in a HT-29 human colon cancer xenograft mouse model. The epithionitrile 1-cyano-2,3-epithiopropane (CETP) was identified as the major active cancer cell-killing principle of L. latifolium. Synthetic and plant-derived CETP displayed similar proapoptotic activities as assessed by biochemical and morphological analyses. Analysis of the antiproliferative capacity of CETP on a wide number of cancer cell lines from the NCI-60 cell line panel followed by COMPARE analysis, showed an activity profile different from known anticancer agents. Flow cytometry and biochemical analyses revealed that CETP-induced apoptosis involved mitochondria, as assessed by loss of mitochondrial transmembrane potential and generation of reactive oxygen species, while overexpression of Bcl-XL and Bcl-2 prevented CETP-induced apoptosis. Inhibition of reactive oxygen species by glutathione and N-acetyl cysteine reduced the apoptotic response induced by CETP. FADD dominant negative form, blocking Fas/CD95 signaling, and a specific caspase-8 inhibitor also inhibited CETP-induced killing. Taken together, our data suggest that the cancer cell-killing action of CETP, involving both intrinsic and extrinsic apoptotic signaling pathways, underlies the antitumor activity of L. latifolium plant, which could be of potential interest in cancer treatment.

Pinnatifidenyne-Derived Ethynyl Oxirane Acetogenins from Laurencia viridis.

Red algae of Laurencia continue to provide wide structural diversity and complexity of halogenated C15 acetogenin medium-ring ethers. Here, we described the isolation of three new C15 acetogenins (3-5), and one truncated derivative (6) from Laurencia viridis collected on the Canary Islands. These compounds are interesting variations on the pinnatifidenyne structure that included the first examples of ethynyl oxirane derivatives (3-4). The structures were elucidated by extensive study of NMR (Nuclear Magnetic Resonance) data, J-based configuration analysis and DFT (Density Functional Theory) calculations. Their antiproliferative activity against six human solid tumor cell lines was evaluated.

Synthesis and biological evaluation of crown ether acyl derivatives.

A set of crown ethyl acyl derivatives based on 18-crown-6 moiety was synthesized and evaluated for biological activity. In vitro antiproliferative profiling demonstrated significant activities against HBL-100, HeLa, SW1573 and WiDr human cell lines. The most active compound exhibited GI50 values in the range of 3.7-5.6µM. Antimicrobial evaluation showed that three polyaromatic compounds were active against Staphylococcus aureus (MIC90 values from 8.3µM to 50µM), whereas a (decyloxy)benzene substitution exhibited moderate activity against Candida albicans (MIC90 values 36µM). According to SAR evaluation, the size of the crown ether and the acyl side chain had a significant effect on the bioactivity. Aromatic moieties close to the acyl group led to improved bioactivity as exemplified by some of the tested compounds. These results provide further evidence on the potential of crown ethyl structure as a scaffold for developing new biological probes and lead candidates for drug development.

Novel role for the midbody in primary ciliogenesis by polarized epithelial cells.

The primary cilium is a membrane protrusion that is crucial for vertebrate tissue homeostasis and development. Here, we investigated the uncharacterized process of primary ciliogenesis in polarized epithelial cells. We show that after cytokinesis, the midbody is inherited by one of the daughter cells as a remnant that initially locates peripherally at the apical surface of one of the daughter cells. The remnant then moves along the apical surface and, once proximal to the centrosome at the center of the apical surface, enables cilium formation. The physical removal of the remnant greatly impairs ciliogenesis. We developed a probabilistic cell population-based model that reproduces the experimental data. In addition, our model explains, solely in terms of cell area constraints, the various observed transitions of the midbody, the beginning of ciliogenesis, and the accumulation of ciliated cells. Our findings reveal a biological mechanism that links the three microtubule-based organelles-the midbody, the centrosome, and the cilium-in the same cellular process.