The polarity protein VANG-1 antagonizes Wnt signaling by facilitating Frizzled endocytosis

Signaling that instructs the migration of neurons needs to be tightly regulated to ensure precise positioning of neurons and subsequent wiring of the neuronal circuits. Wnt-Frizzled signaling controls neuronal migration in metazoans, in addition to many other aspects of neural development. We show that Caenorhabditis elegans VANG-1, a membrane protein that acts in the planar cell polarity (PCP) pathway, antagonizes Wnt signaling by facilitating endocytosis of the Frizzled receptors. Mutations of vang-1 suppress migration defects of multiple classes of neurons in the Frizzled mutants, and overexpression of vang-1 causes neuronal migration defects similar to those of the Frizzled mutants. Our genetic experiments suggest that VANG-1 facilitates Frizzled endocytosis through β-arrestin2. Co-immunoprecipitation experiments indicate that Frizzled proteins and VANG-1 form a complex, and this physical interaction requires the Frizzled cysteine-rich domain. Our work reveals a novel mechanism mediated by the PCP protein VANG-1 that downregulates Wnt signaling through Frizzled endocytosis

同時送信型無線ネットワークの物理層に関する研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 森川 博之, 東京大学教授 相田 仁, 東京大学教授 廣瀬 明, 東京大学准教授 中山 雅哉, 東京大学准教授 落合 秀也University of Tokyo(東京大学

The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten regulates focal adhesion localization and growth suppression activity of DLC-1

The tensin family member cten (C-terminal tensin like) is an Src homology 2 (SH2) and phosphotyrosine binding domain–containing focal adhesion molecule that may function as a tumor suppressor. However, the mechanism has not been well established. We report that cten binds to another tumor suppressor, deleted in liver cancer 1 (DLC-1), and the SH2 domain of cten is responsible for the interaction. Unexpectedly, the interaction between DLC-1 and the cten SH2 domain is independent of tyrosine phosphorylation of DLC-1. By site-directed mutagenesis, we have identified several amino acid residues on cten and DLC-1 that are essential for this interaction. Mutations on DLC-1 perturb the interaction with cten and disrupt the focal adhesion localization of DLC-1. Furthermore, these DLC-1 mutants have lost their tumor suppression activities. When these DLC-1 mutants were fused to a focal adhesion targeting sequence, their tumor suppression activities were significantly restored. These results provide a novel mechanism whereby the SH2 domain of cten-mediated focal adhesion localization of DLC-1 plays an essential role in its tumor suppression activity

The polarity protein VANG-1 antagonizes Wnt signaling by facilitating Frizzled endocytosis

Signaling that instructs the migration of neurons needs to be tightly regulated to ensure precise positioning of neurons and subsequent wiring of the neuronal circuits. Wnt-Frizzled signaling controls neuronal migration in metazoans, in addition to many other aspects of neural development. We show that Caenorhabditis elegans VANG-1, a membrane protein that acts in the planar cell polarity (PCP) pathway, antagonizes Wnt signaling by facilitating endocytosis of the Frizzled receptors. Mutations of vang-1 suppress migration defects of multiple classes of neurons in the Frizzled mutants, and overexpression of vang-1 causes neuronal migration defects similar to those of the Frizzled mutants. Our genetic experiments suggest that VANG-1 facilitates Frizzled endocytosis through β-arrestin2. Co-immunoprecipitation experiments indicate that Frizzled proteins and VANG-1 form a complex, and this physical interaction requires the Frizzled cysteine-rich domain. Our work reveals a novel mechanism mediated by the PCP protein VANG-1 that downregulates Wnt signaling through Frizzled endocytosis

Refractory gastric variceal bleeding secondary to splenic vein occlusion associated with abdominal lymphadenopathy

SummarySplenic vein occlusion caused by abdominal lymphadenopathy is rare. We herein present the case of a 80-year-old man with refractory isolated gastric variceal bleeding in the absence of pancreatic or liver disease. Left-sided portal hypertension was confirmed by angiography, and para-aortic lymphadenopathy compressing the splenic vein was identified by serial abdominal computed tomography. Endoscopic sclerosing therapy failed to treat the recurring gastric variceal hemorrhage. Therefore, splenectomy was suggested and the patient was successfully treated. The patient had been variceal bleeding free for 12 months since the surgery. In patients with isolated gastric varices but without advanced liver disease, a variety of diagnostic techniques should be attempted to elucidate the nature of portal hypertension, and left-sided portal hypertension should be suspected. For those cases in which endoscopic treatment failed to treat refractory gastric variceal bleeding, splenectomy can be an effective option

Role of the Diphosphine Chelate in Emissive, Charge-Neutral Iridium(III) Complexes

A class of neutral tris-bidentate Ir(III) metal complexes incorporating a diphosphine as a chelate is prepared and characterized here for the first time. Treatment of [Ir(dppb)(tht)Cl3] (1) with fppzH afforded the dichloride complexes, trans-(Cl,Cl)[Ir(dppb)(fppz)Cl2] (2) and cis-(Cl,Cl)[Ir(dppb)(fppz)Cl2] (3). The reaction of 3 with the dianionic chelate precursor bipzH2 or mepzH2, in DMF gave the complex [Ir(dppb)(fppz)(bipz)] (4) or [Ir(dppb)(fppz)(mepz)] (5), respectively. In contrast, a hydride complex [Ir(dppb)(fppz)(bipzH)H] (6) was isolated instead of 4 in protic solvent, namely: DGME. All complexes 2 - 6 are luminescent in powder forms and thin films where the dichlorides (2, 3) emit with maxima at 590-627 nm (orange) and quantum yields (Q.Y.s) up to 90% whereas the tris-bidentate (4, 5) and hydride (6) complexes emit at 455-458 nm (blue) with Q.Y.s up to 70%. Hybrid TD-DFT calculations showed considerable MLCT contribution to the orange-emitting 2 and 3 but substantial ligand-centered 3ππ* transition character in the blue-emitting 4 - 6. The dppb does not participate to these radiative transitions in 4 - 6, but it provides the rigidity and steric bulk needed to promote the luminescence by suppressing the self-quenching in the solid state. Fabrication of an OLED with dopant 5 gave a deep blue CIE chromaticity of (0.16, 0.15). Superior blue emitters, which are vital in OLED applications, may be found in other neutral Ir(III) complexes containing phosphine chelates

Prevalence of depressive tendencies among college students and the influence of attributional styles on depressive tendencies in the post-pandemic era

IntroductionDepression symptoms are prevalent globally, including China, with a notable impact on college students. This study aims to not only estimate the prevalence of depressive tendencies and attributional styles among college students in the post-pandemic era but also explore the relationship between the two factors. The findings of this study can provide new insights into early intervention and support services for individuals exhibiting tendencies toward depression.MethodsThe survey was administered to college students from various academic backgrounds at a specific university in southern Jiangxi Province by employing two scales to investigate depressive tendencies and attributional styles. Depressive tendency was evaluated using the Patient Health Questionnaire-9 (PHQ-9), while the attributional styles were assessed using the Multidimensional-Multiattributional Causality Scale (MMCS). Univariate analysis and multiple logistic regressions were conducted to identify the related factors of depressive tendency.ResultsA relatively high (48.9%) prevalence of depression among college students was found in this study. College students with higher grades (OR = 1.574, 95%CI: 1.369–1.810), profession of medicine and allied health sciences (OR = 1.779, 95%CI: 1.203–2.629), experiencing higher study stress (OR = 2.006, 95%CI: 1.601–2.514), and having poor physical condition (OR = 1.527, 95%CI: 1.247–1.869) were identified as risk factors for depressive tendency. The correlation between higher grades and increased learning pressure, coupled with poorer physical condition, heightens the vulnerability of college students to depression. Moreover, the more they attribute these experiences to achievement effort (OR = 0.897, 95%CI: 0.828–0.972), achievement ability (OR = 0.903, 95%CI: 0.838–0.972), and affiliation context (OR = 0.919, 95%CI: 0.860–0.982), the less likely they are to develop depression.ConclusionIn the group of college students, especially those in higher grades, profession of medicine and allied health sciences or experiencing high learning pressure and poor physical condition, emphasizing the significance of their mental well-being becomes crucial. Offering suitable support and assistance is essential. Additionally, fostering the cultivation of positive attributional and coping strategies by attributing difficulties to controllable factors and instilling a belief in their ability to overcome challenges can help reduce the risk of depression

Persistent surgical wound bleeding: A rare condition related to acquired hemophilia A

SummaryAcquired hemophilia A (AHA) is a rare condition that predisposes affected patients to a bleeding tendency, even after a trivial physical insult. We present our experience with a 45-year-old male patient who was referred to our institute because of persistent bleeding from a left forearm surgical wound after fasciotomy. He was diagnosed as having AHA. Surgical treatment in combination with recombinant activated factor VII (rFVIIa) led to a satisfactory result. Clinical awareness and multidisciplinary professional connections are necessary in the treatment of AHA. Acquired hemophilia should be considered in the differential diagnosis of patients with uncontrolled bleeding episodes