NuMA assemblies organize microtubule asters to establish spindle bipolarity in acentrosomal human cells.

In most animal cells, mitotic spindle formation is mediated by coordination of centrosomal and acentrosomal pathways. At the onset of mitosis, centrosomes promote spindle bipolarization. However, the mechanism through which the acentrosomal pathways facilitate the establishment of spindle bipolarity in early mitosis is not completely understood. In this study, we show the critical roles of nuclear mitotic apparatus protein (NuMA) in the generation of spindle bipolarity in acentrosomal human cells. In acentrosomal human cells, we found that small microtubule asters containing NuMA formed at the time of nuclear envelope breakdown. In addition, these asters were assembled by dynein and the clustering activity of NuMA. Subsequently, NuMA organized the radial array of microtubules, which incorporates Eg5, and thus facilitated spindle bipolarization. Importantly, in cells with centrosomes, we also found that NuMA promoted the initial step of spindle bipolarization in early mitosis. Overall, these data suggest that canonical centrosomal and NuMA-mediated acentrosomal pathways redundantly promote spindle bipolarity in human cells.

2D Memory Selectors with Giant Nonlinearity Enabled by Van der Waals Heterostructures.

The integration of one-selector-one-resistor crossbar arrays requires the selectors featured with high nonlinearity and bipolarity to prevent leakage currents and any crosstalk among distinct cells. However, a selector with sufficient nonlinearity especially in the frame of device miniaturization remains scarce, restricting the advance of high-density storage devices. Herein, a high-performance memory selector is reported by constructing a graphene/hBN/WSe2 heterostructure. Within the temperature range of 300-80 K, the nonlinearity of this selector varies from ≈103 - ≈104 under forward bias, and increases from ≈300 - ≈105 under reverse bias, the highest reported nonlinearity among 2D selectors. This improvement is ascribed to direct tunneling at low bias and Fowler-Nordheim tunneling at high bias. The tunneling current versus voltage curves exhibit excellent bipolarity behavior because of the comparable hole and electron tunneling barriers, and the charge transport polarity can be effectively tuned from N-type or P-type to bipolar by simply changing source-drain bias. In addition, the conceptual memory selector exhibits no sign of deterioration after 70 000 switching cycles, paving the way for assembling 2D selectors into modern memory devices.

Unmasking bipolarity in recurrent depressive disorder following herpes simplex virus triggered n-methyl-D-aspartate encephalitis.

OBJECTIVE: Herpes simplex virus (HSV) infection triggered n-methyl-D-aspartate (NMDA) encephalitis can lead to varied neuropsychiatric manifestations, including movement disorders and manic symptoms. HSV is known to affect the same brain regions as in secondary mania. METHOD: We present a 35-year-old female diagnosed with recurrent depressive disorder (RDD) who developed NMDA encephalitis triggered by HSV infection. RESULT: HSV-triggered NMDA encephalitis led to a manic switch in a woman with RDD on antidepressants, along with the new onset of dyskinetic movements. CONCLUSION: A neurological insult predisposed our patient to the variable effects of antidepressant drugs.

Multielectron Redox-Bipolar Tetranitroporphyrin Macrocycle Cathode for High-Performance Zinc-Organic Batteries.

Bipolar organics fuse the merits of n/p-type redox reactions for better Zn-organic batteries (ZOBs), but face the capacity plafond due to low density of active units and single-electron reactions. Here we report multielectron redox-bipolar tetranitroporphyrin (TNP) with quadruple two-electron-accepting n-type nitro motifs and dual-electron-donating p-type amine moieties towards high-capacity-voltage ZOBs. TNP cathode initiates high-kinetics, hybrid anion-cation 10e- charge storage involving four nitro sites coordinating with Zn2+ ions at low potential and two amine species coupling with SO4 2- ions at high potential. Consequently, Zn||TNP battery harvests high capacity (338 mAh g-1), boosted average voltage (1.08 V), and outstanding energy density (365 Wh kg-1 TNP). Moreover, the extended π-conjugated TNP macrocycle achieves anti-dissolution in electrolytes, prolonging the battery life to 50,000 cycles at 10 A g-1 with 71.6 % capacity retention. This work expands the chemical landscape of multielectron redox-bipolar organics for state-of-the-art ZOBs.

[Questioning disruptive disorder with emotional dysregulation]. / Questionner le trouble disruptif avec dysrégulation émotionnelle.

Disruptive Emotional Dysregulation Disorder (DEDD) responds to an increase in diagnoses of clastic crises, reactive depression and bipolarity in children and adolescents. Emerging in the 1990s, EDD has become an issue for practitioners, parents and teachers alike, and has become an integral part of the landscape of paediatric and child psychiatric disorders. Its diagnostic complexity is accentuated by criteria that include persistent and disproportionate outbursts of anger, often confused with other pathologies, especially as diagnostic tools are few and far between. Professionals in the field know little about EDD, preferring to diagnose more familiar disorders.

Ion transport properties in the pH-dependent bipolar nanochannels.

In recent years, researchers have made significant strides in understanding the ion transport characteristics of nanochannels, resulting in the development of various materials, modifications, and shapes of nano ion channel membranes. The aim is to create a nanochannel membrane with optimal ion transport properties and high stability by adjusting factors, such as channel size, surface charge, and wettability. However, during the nanochannel film fabrication process, controlling the geometric structures of nanochannels can be challenging. Therefore, exploring the stability of nanochannel performance under different geometric structures has become an essential aspect of nanochannel design. This article focuses on the study of cylindrical nanochannel structures, which are categorized based on the different methods for generating bipolar surface charges on the channel's inner surface, either through pH gradient effects or different material types. Through these two approaches, the study designed and analyzed the stability of ion transport characteristics in two nanochannel models under varying geometric structures. Our findings indicate that nanochannels with bipolar properties generated through pH gradients demonstrate more stable ion selection, whereas nanochannels with bipolar properties generated through different materials show stronger stability in ion rectification. This conclusion provides a theoretical foundation for future nanochannel designs.

Assessment of the spectrum of depression and bipolarity in patients with type 1 diabetes.

AIMS: The aim of the study was to check the prevalence of unipolarity (depression), bipolarity, as well as the quality of sleep and temperament traits in patients with type 1 diabetes (T1DM) who are provided with optimal conditions of diabetes care and to identify possible risk factors connected with affective traits. MATERIALS AND METHODS: Out of the 107 T1DM patients, 78 (54 females, 24 males) were included for the analysis (HbA1c [%] 7.11 ± 1.0, BMI [kg/m2 ] 25.3 ± 5.6; Years of disease duration [N] 13.7 ± 8.3). The patients filled in a set of questionnaires during their regular visit to the outpatient clinic. Three patients from the whole group were on intensive insulin therapy with Multiple Daily Injections (MDI) and Self-Monitoring of Blood Glucose (SMBG), all the rest were on various types of personal insulin pumps (years on insulin pump [N] 9.1 ± 4.5). All the patients were on regular diabetologist care, with regular visits in a Centre for Advanced Technologies in Diabetes (at least every 6 months). RESULTS: In QIDS-S (full explanation and abbreviation 26 patients (33.8%) were screened positive for depression, in PHQ (full explanation and ab 57.7% of the patients (45 patients) had symptoms of depression (age was negatively correlated with PHQ score [r = -0.26; p = 0.023]). In CES-D 16 (20%) of the patients assessed their present affect as depressed. None of the analysed clinical variables correlated with depression scores. In the Mood Disorder Questionnaire (MDQ), 16 patients reported having symptoms of bipolarity (20.5% vs. 79.5%). Hypomania Checklist (HCL) analysis indicated 10 patients with bipolar traits (>14) (14.9% vs. 85.1%). None of the analysed clinical variables correlated with HCL results. 11.5% of patients were indicated to be of morning type. Morningness was more often seen in younger patients (r = 0.39; p = 0.001). As many as 46.6% declared that they had poor sleep quality. The temperament traits analysis correlated with clinical parameters: Cyclothymic temperament trait was negatively correlated with age (r = -0.30; p = 0.007) and positively with HbA1c level (r = 0.30; p = 0.025). Hyperthymic temperament was positively correlated with (BMI r = 0.28; p = 0.016). Quality of sleep was highly correlated with depressive symptoms CESD (r = 0.61, p = 0.001), PHQ Score (r = 0.62; p = 0.001), QISD (r = 0.68; p = 0.001) and bipolarity MDQ (p = 0.50, p = 0.001) and HCL (r = 0.42, p = 0.001). In addition, QIDS was shown to be correlated with the following features of temperament: depressive factor (r = 0.41; p = 0.001), irritable factor (r = 0.53; p = 0.001), cyclothymic factor (r = 0.59; p = 0.001), anxious factor (r = 0.58, p = 0.001). CONCLUSIONS: The prevalence of affective disorders and poor sleep quality in the examined T1DM patients was much higher than in the general population. Even if the patients have in general good glycaemic control, their mental health condition should not be neglected. Well organised cooperation between patients, diabetologists, psychiatrists and psychotherapists is needed (Clinical Trials Identifier: NCT04616391).

Identifying the bridge between depression and mania: A machine learning and network approach to bipolar disorder.

OBJECTIVES: Although the cyclic nature of bipolarity is almost by definition a network system, no research to date has attempted to scrutinize the relationship of the two bipolar poles using network psychometrics. We used state-of-the-art network and machine learning methodologies to identify symptoms, as well as relations thereof, that bridge depression and mania. METHODS: Observational study that used mental health data (12 symptoms for depression and 12 for mania) from a large, representative Canadian sample (the Canadian Community Health Survey of 2002). Complete data (N = 36,557; 54.6% female) were analysed using network psychometrics, in conjunction with a random forest algorithm, to examine the bidirectional interplay of depressive and manic symptoms. RESULTS: Centrality analyses pointed to symptoms relating to emotionality and hyperactivity as being the most central aspects of depression and mania, respectively. The two syndromes were spatially segregated in the bipolar model and four symptoms appeared crucial in bridging them: sleep disturbances (insomnia and hypersomnia), anhedonia, suicidal ideation, and impulsivity. Our machine learning algorithm validated the clinical utility of central and bridge symptoms (in the prediction of lifetime episodes of mania and depression), and suggested that centrality, but not bridge, metrics map almost perfectly onto a data-driven measure of diagnostic utility. CONCLUSIONS: Our results replicate key findings from past network studies on bipolar disorder, but also extend them by highlighting symptoms that bridge the two bipolar poles, while also demonstrating their clinical utility. If replicated, these endophenotypes could prove fruitful targets for prevention/intervention strategies for bipolar disorders.

A Focus on Enterochromaffin Cells among the Enteroendocrine Cells: Localization, Morphology, and Role.

The intestinal epithelium plays a key role in managing the relationship with the environment, the internal and external inputs, and their changes. One percent of the gut epithelium is represented by the enteroendocrine cells. Among the enteroendocrine cells, a group of specific cells characterized by the presence of yellow granules, the enterochromaffin cells, has been identified. These granules contain many secretion products. Studies showed that these cells are involved in gastrointestinal inflammatory conditions and hyperalgesia; their number increases in these conditions both in affected and not-affected zones of the gut. Moreover, they are involved in the preservation and modulation of the intestinal function and motility, and they sense metabolic-nutritional alterations. Sometimes, they are confused or mixed with other enteroendocrine cells, and it is difficult to define their activity. However, it is known that they change their functions during diseases; they increased in number, but their involvement is related mainly to some secretion products (serotonin, melatonin, substance P). The mechanisms linked to these alterations are not well investigated. Herein, we provide an up-to-date highlight of the main findings about these cells, from their discovery to today. We emphasized their origin, morphology, and their link with diet to better evaluate their role for preventing or treating metabolic disorders considering that these diseases are currently a public health burden.

How significant is the assessment of the DSM-5 'anxious distress' specifier in patients with major depressive disorder without comorbid anxiety disorders in the continuation/maintenance phase?

OBJECTIVE: Anxious distress (ANXD), which is common in major depressive disorder (MDD), is associated with poor outcomes. We investigated clinical characteristics of MDD patients with the DSM-5 ANXD specifier and only mild residual symptoms without comorbid anxiety disorders in the continuation/maintenance phase. METHODS: We recruited 110 outpatients with MDD without comorbid anxiety disorders. They were interviewed; the presence of the DSM-5 ANXD specifier was assessed. They completed the Quick Inventory of Depressive Symptomatology (QIDS), the Eysenck Personality Questionnaire (S-EPQ), the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). RESULTS: The mean QIDS total score was 9.7 ± 5.5. The DSM-5 ANXD specifier was identified in 73 patients (66.4%). A univariate analysis indicated ANXD was significantly associated with younger age; unmarried status; living alone; higher QIDS total score; higher S-EPQ neuroticism score; and higher TEMPS-A cyclothymic, depressive and irritable scores. After covariate adjustment, a multivariable linear regression analysis revealed a significant association between the QIDS total score and ANXD (three different models). CONCLUSION: The DSM-5 ANXD was also common among MDD patients without comorbid anxiety disorders in the continuation/maintenance phase; it was significantly associated with greater depression severity and might be related to temperament associated with bipolar disorder.Key pointsDSM-5 anxious distress is common among MDD patients without comorbid anxiety disorders in the continuation/maintenance phase and correlated with some of their socio-demographic and clinical characteristics. • The presence of DSM-5 anxious distress was significantly associated with greater severity of depression and might be related to temperament associated with bipolar disorder.• The evaluation of the DSM-5 anxiety distress was revealed to have some significance not only in the acute phase but also in the continuation/maintenance phase of MDD.

Centrosomal and Non-centrosomal Functions Emerged through Eliminating Centrosomes.

Centrosomes are highly conserved organelles that act as the major microtubule-organizing center (MTOC) in animal somatic cells. Through their MTOC activity, centrosomes play various roles throughout the cell cycle, such as supporting cell migration in interphase and spindle organization and positioning in mitosis. Various approaches for removing centrosomes from somatic cells have been developed and applied over the past few decades to understand the precise roles of centrosomes. Centrinone, a reversible and selective PLK4 (polo-like kinase 4) inhibitor, has recently emerged as an efficient approach to eliminate centrosomes. In this review, we describe the latest findings on centrosome function that have been revealed using various centrosome-eliminating approaches. In addition, we discuss our recent findings on the mechanism of centrosome-independent spindle bipolarization, discovered through the use of centrinone.Key words: centrosome, centrinone, mitotic spindle, bipolarity, NuMA.

Stalin's "black dog": a postmortem diagnosis.

Undoubtedly, the two leaders who were under enormous pressure during World War II (WWII) were Winston Churchill and Joseph Stalin' since their respective countries had to sustain most of the war weight, at least in Europe. Lord Moran recounted in his memoir Winston Churchill: The Struggle for Survival that he had diagnosed a middle-aged Churchill with bipolar disorder. Churchill himself often referred to his periods of intense and prolonged depression as his "black dog." On the contrary, not much is known about Stalin's mental conditions, although in 1927 the neurologist V. M. Bekhterev, the day prior to his sudden death, upon a long examination of the leader's mental status, declared that he had found him affected by paranoia. No chemical evidence via clinical chemistry analyses was provided for the two leaders, though. We have had access to the collection of books (stored in the Russian Government Archive of Social and Political History, RGASPI, of the former Institute of Marxism and Leninism under the Central Committee of the USSR Communist Party) that Stalin was reading during WWII, with pages containing personal annotations on the margins. Upon harvesting surface material via EVA disks (ethylene-vinyl acetate studded with strong cation and anion exchangers and C8-C18 resins) and instrumental analysis via X-ray photoelectron spectroscopy, we detected lithium levels (~ 100 ± 8 ng/cm2) compatible with those present in the sweat and/or saliva of patients treated with lithium salts for curing bipolarity and paranoia or probably gout. These data are the first clear indication that Stalin was under cure for this pathology.Graphical abstract.

Creativity and positive psychology in psychotherapy.

Creativity is the ability to produce something novel and useful that is a valuable contribution to a specific domain. It is a significant common factor in most forms of psychotherapy. Accordingly, it is essential to investigate its role both in psychotherapy in general and in specific approaches like relational, cognitive-behavioural, psychodynamic, systemic, and existential psychotherapy. Positive psychology in particular has pointed up the usefulness of creativity in psychotherapy. Here we draw upon a case example to show how the creative discovery of novel and useful solutions takes place in different dimensions: relational, behavioural, psychodynamic, systemic and existential. The case description demonstrates how principles of positive psychology are useful in many realms of psychotherapy. We propose an integrated model of psychotherapy that brings together different psychotherapeutic methods and is based on interdisciplinary creativity research. The integration of neuroscientific, psychological and cultural findings produced by creativity research can be expected to lead to a deeper understanding of psychotherapeutic, positive-psychological, and creative processes.

TP53BP1 regulates chromosome alignment and spindle bipolarity in mouse oocytes.

Meiotic oocytes lack classic centrosomes; therefore, bipolar spindle assembly depends on the clustering of acentriolar microtubule-organizing centers (MTOCs) into two poles. The bipolar spindle is an essential cellular component that ensures accurate chromosome segregation during anaphase. If the spindle does not form properly, it can result in aneuploidy or cell death. However, the molecular mechanism by which the bipolar spindle is established is not yet fully understood. Tumor suppressor p53-binding protein 1 (TP53BP1) is known to mediate the DNA damage response. Several recent studies have indicated that TP53BP1 has noncanonical roles in processes, such as spindle formation; however, the role of TP53BP1 in oocyte meiosis is currently unclear. Our results show that TP53BP1 knockdown affects spindle bipolarity and chromatin alignment by altering MTOC stability during oocyte maturation. TP53BP1 was localized in the cytoplasm and displayed an irregular cloud pattern around the spindle/chromosome region. TP53BP1 was also required for the correct localization of MTOCs into the two spindle poles during pro-meiosis I. TP53BP1 deletion altered the MTOC-localized Aurora Kinase A. TP53BP1 knockdown caused the microtubules to detach from the kinetochores and increased the rate of aneuploidy. Taken together, our data show that TP53BP1 plays crucial roles in chromosome stability and spindle bipolarity during meiotic maturation.

Poor emotion regulation ability mediates the link between depressive symptoms and affective bipolarity.

People's relationship between positive and negative affect varies on a continuum from relatively independent to bipolar opposites, with stronger bipolar opposition being termed affective bipolarity. Experiencing more depressive symptoms is associated with increased bipolarity, but the processes underlying this relation are not yet understood. Here, we sought to replicate this link, and to examine the role of two potential mediating mechanisms: emotion regulation ability, and trait brooding. Drawing from the Dynamic Model of Affect, we hypothesised that (a) a poor ability to regulate negative emotion, and (b) the tendency to brood over one's depressed feelings would predict stronger affective bipolarity, and mediate the relationship between depressive symptoms and affective bipolarity. To measure affective bipolarity, we calculated within-person affect correlations using two weeks of experience sampling data from a community sample (n = 100). Mediation analyses indicated that baseline assessments of an inability to regulate negative emotions in general, but not brooding specifically, mediated the relation between depressive symptoms and affective bipolarity. These findings highlight an initial mechanism through which depressive symptoms are associated with lower emotional complexity and flexibility.

Political terrorism and affective polarization in "black" and "red" terrorists in Italy during the years 1968-1988.

Psychiatric evaluations of violent political crime were mostly performed on a case-by-case basis in a forensic environment, which made them unduly dependent on categories of presumed dangerousness and legal responsibility, rather than on a clinical definition of their mental status. In referring to such "clinical" definitions, the disorder we have in mind is not limited to the major, agitated psychotic manias or mixed states. The presence of a dominant temperament, or protracted hypomania, is enough by itself to explain an individual's engagement in a wide range of activities, not necessarily sociopathic or violent. We put forward the hypothesis that formal and transpolitical radical choices, either in favor of an illegal lifestyle or of activities involving a high level of risk, may be linked with certain mental states, especially when considering small clandestine groups showing a high level of internal ideological consensus, and a no-return attitude toward a commitment to radical choices. Available data about the psycho(patho)logical profile of terrorists are still hard to come by. The only available studies are those on identified living terrorists (judging by the trials of those who personally admitted to having been terrorists), and statistical data imply a number of documented cases belonging to the same terrorist organization. In Italy, the period often called the "years of lead [bullets]" displays an interesting viewpoint for the study of terrorist psychology, for two main reasons: first of all, it is a historically defined period (1968-1988), and second, the number of ascertained participants in terrorist activities was quite large.

Personality traits and maladaptivity: Unipolarity versus bipolarity.

OBJECTIVE: Dimensional personality trait models have gained favor as an alternative to categorical personality disorder (PD) diagnosis; however, debate persists regarding whether these traits should be conceptualized as maladaptive at both extremes (i.e., maladaptively bipolar) or just one trait pole (i.e., unipolar). METHOD: To inform the debate on maladaptive bipolarity, linear and nonlinear relations between personality traits and dysfunction were examined in a large psychiatric patient sample (N = 365). Participants self-reported on normal-range and pathological personality domains, life satisfaction, specific interpersonal problems, and broad psychosocial functioning. In addition, participants were interviewed regarding specific psychiatric symptoms and broad psychosocial functioning. RESULTS: All traits related moderately to strongly with at least one dysfunction variable. All traits were predominantly correlated with dysfunction at one pole; however, several small linear relations provided some evidence for maladaptively high Extraversion and Agreeableness. None of the significant nonlinear effects provided clear evidence for maladaptivity at both ends of any trait. CONCLUSIONS: Taken together, these results suggest that broad personality traits are predominantly maladaptive at one extreme; however, in limited cases, the opposite extreme may also be maladaptive.

Obesity in patients with major depression is related to bipolarity and mixed features: evidence from the BRIDGE-II-Mix study.

OBJECTIVES: The Bipolar Disorders: Improving Diagnosis, Guidance and Education (BRIDGE)-II-Mix study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions. The present post-hoc analysis evaluated the association between obesity and the presence of mixed features and bipolarity. METHODS: A total of 2811 MDE subjects were enrolled in a multicenter cross-sectional study. In 2744 patients, the body mass index (BMI) was evaluated. Psychiatric symptoms, and sociodemographic and clinical variables were collected, comparing the characteristics of MDE patients with (MDE-OB) and without (MDE-NOB) obesity. RESULTS: Obesity (BMI ≥30) was registered in 493 patients (18%). In the MDE-OB group, 90 patients (20%) fulfilled the DSM-IV-TR criteria for bipolar disease (BD), 225 patients (50%) fulfilled the bipolarity specifier criteria, 59 patients (13%) fulfilled DSM-5 criteria for MDEs with mixed features, and 226 patients (50%) fulfilled Research-Based Diagnostic Criteria for an MDE. Older age, history of (hypo)manic switches during antidepressant treatment, the occurrence of three or more MDEs, atypical depressive features, antipsychotic treatment, female gender, depressive mixed state according to DSM-5 criteria, comorbid eating disorders, and anxiety disorders were significantly associated with the MDE-OB group. Among (hypo)manic symptoms during the current MDE, psychomotor agitation, distractibility, increased energy, and risky behaviors were the variables most frequently associated with MDE-OB group. CONCLUSIONS: In our sample, the presence of obesity in patients with an MDE seemed to be associated with higher rates of bipolar spectrum disorders. These findings suggest that obesity in patients with an MDE could be considered as a possible marker of bipolarity.

Bipolar Disorder and/or Creative Bipolarity: Robert Schumann's Exemplary Psychopathology - Combining Symptomatological and Psychosocial Perspectives with Creativity Research.

The psychopathological condition of Robert Schumann has been a prominent object of study in psychiatry since his hospitalization in 1854. Renowned psychiatrists have diagnosed Schumann with syphilis, schizophrenia, and bipolar and personality disorders. Until today, these analyses of his symptomatology have led to contradictory results. Recent discussion has suggested that his hospitalization was due to professional failure and separation wishes on the part of his wife, her family, and her friends. In line with this hypothesis is the opinion that the separation insisted upon by Clara Schumann was reinforced by the economic interests of the psychiatrist who kept Schumann in custody for 2 years until his death in 1856. In this article, we trace the complex interaction of bipolar vulnerability and pathogenic life events with hypersensitive talent and "creative bipolarity," defined as the capacity, motivation, and resilience to transform emotional stress and cognitive inconsistency into coherent artistic products. Finally, we present our conclusions about comprehensive psychiatric and psychotherapeutic treatment with respect to "creative bipolarity."

Tubulogenesis in a simple cell cord requires the formation of bi-apical cells through two discrete Par domains.

Apico-basal polarization is a crucial step in the de novo formation of biological tubes. In Ciona notochord, tubulogenesis occurs in a single file of cells in the absence of cell proliferation. This configuration presents a unique challenge for the formation of a continuous lumen. Here, we show that this geometric configuration is associated with a novel polarization strategy: the generation of bipolar epithelial cells possessing two apical/luminal domains instead of one, as in the conventional epithelium. At the molecular level, cells establish two discrete Par3/Par6/aPKC patches, and form two sets of tight junctions, in opposite points of the cells. The key molecule controlling the formation of both domains is Par3. Changing the position of the cells within the organ fundamentally changes their polarity and the number of apical domains they develop. These results reveal a new mechanism for tubulogenesis from the simplest cell arrangement, which occurs in other developmental contexts, including vertebrate vascular anastomosis.