Ca2+/Calmodulin induces translocation of membrane-associated TSC2 to the nucleus where it suppresses CYP24A1 expression.

Tuberous sclerosis complex 2 (TSC2) is a tumor-suppressor protein. A loss of TSC2 function induces hyperactivation of mechanistic target of rapamycin (mTOR). The C-terminal region of TSC2 contains a calmodulin (CaM) binding region and the CaM-TSC2 interaction contributes to proper mTOR activity. However, other downstream signaling pathways/effectors activated by the CaM-TSC2 complex have not been fully elucidated. In this study, we found that activation of Ca2+/CaM signaling resulted in the translocation of membrane-associated TSC2 to the nucleus and suppressed the transcriptional activity of the vitamin D receptor (VDR). TSC2 was released from the membrane in an activated CaM-dependent state in rat brain and HeLa cells. It subsequently formed a transcriptional complex to partially suppress the transcription of CYP24A1, a well-known VDR target gene. These data suggest, in part, that TSC2 attenuates VDR-associated transcriptional regulation via Ca2+/CaM signaling.

A fact-finding survey on self-efficacy of foot care behaviour in patients with diabetes: Analysis using the Diabetes Study from the Center of Tokyo Women's Medical University 2017 (DIACET 2017).

Aim: We aimed to determine the association between self-efficacy of foot care behaviour and chronic complications in Japanese patients with diabetes. Methods: We conducted a cross-sectional study based on a questionnaire survey of 4571 patients with type 1 and type 2 diabetes who had (a) given consent to participate in the Diabetes Study from the Center of Tokyo Women's Medical University: DIACET 2017, and (b) completed all the questions of the Japanese Version of Foot Care Confidence Scale (J-FCCS), consisting of 12 statements. Results: A greater proportion of respondents answered that they were not confident in determining the condition of corns and/or calluses and the condition of toenails. The J-FCCS total scores of the patients with retinopathy (p <.001) and numbness or pain in the feet (p <.001) were significantly lower than those of the patients without these complications. In both the multiple regression analysis and logistic regression analysis, lower J-FCCS was significantly associated with retinopathy and numbness or pain in the feet. Conclusion: Foot care education that emphasizes a psychological approach in improving confidence associated with foot self-care is important for patients with advanced complications of diabetes.

Type 1 Diabetes, ACTH Deficiency, and Hypothyroidism Simultaneously Induced by Nivolumab Therapy in a Patient with Gastric Cancer: A Case Report.

Nivolumab, a fully human IgG4 immune checkpoint inhibitor (ICI) antibody, has been approved for a variety of cancers. Several endocrine-associated immune-related adverse events have been reported, but the incidence rate is relatively low. This is a case of a patient with gastric cancer who underwent nivolumab therapy, leading to type 1 diabetes as well as adrenocorticotropic hormone (ACTH) deficiency and hypothyroidism almost simultaneously. A 70-year-old man with no previous history of diabetes was treated with nivolumab monotherapy for gastric cancer in November 2018. After 8 courses of nivolumab, he was diagnosed with type 1 diabetes associated with ICI; consequently, insulin therapy was initiated in March 2019. In April 2019, he was transported to hospital due to suffering from prolonged hypoglycemia, disturbed consciousness, and fever. He frequently experienced episodes of hypoglycemia, with poor controlled glycemia. His disturbed consciousness and fever also sustained. Further investigation of his hormones revealed low cortisol and ACTH levels, as well as hypothyroidism. His blood glucose control was improved after the introduction of hydrocortisone and thyroid hormone; he became alert and afebrile. In January 2020, he received a followed-up in an outpatient setting under insulin, hydrocortisone, and thyroid replacement therapy. Endocrine defect associated with ICIs, especially type 1 diabetes or ACTH deficiency, is a rare condition. To the best of our knowledge, this is the 1st case of multiple endocrinopathies simultaneously induced by nivolumab. Various endocrine concomitant defects should be taken into consideration when treating with nivolumab.

Stability and bifurcation analysis of a ratio-dependent community dynamics model on Batesian mimicry.

Batesian mimicry is the similarity of coloration and patterns in an unpalatable species (the "model-species") and a palatable species (the "mimic-species"). The resemblance is advantageous for the mimic-species because the mimic-species can deceive predators and avoid predation. While Batesian mimicry is an important subject in ecology as a general phenomenon in nature, previous theoretical studies focus mainly on the evolution of mimicry and the predator learning process. In these mathematical models, the population sizes of the model- and mimic-species are not considered explicitly or are assumed to be constant, but this is not plausible in model-mimic community dynamics. Thus, the model-mimic community has been paid relatively less attention; However, to elucidate problems on Batesian mimicry, it is essential to understand the fundamental characteristics of the model-mimic community dynamics. Here, we construct a basic model-mimic community dynamics model, obtain the existence and stability conditions of its equilibria, and conduct the bifurcation analysis and numerical calculation. The results show that the instability of the model-only population is predicted, and this is consistent with the typical pattern of geographical distribution in Batesian mimicry in the field. We propose three new hypotheses to explain the typical pattern of geographical distribution. Furthermore, we reveal an irreversibility regarding the model-mimic coexistence that is important for the conservation of the model- and mimic-species.