ExploRing Persistence in Financial Time Series

Edited by W. Härdle, Z. Hlávka, and S. Klinke</p

Synaptic Wnt signaling—a contributor to major psychiatric disorders?

Wnt signaling is a key pathway that helps organize development of the nervous system. It influences cell proliferation, cell fate, and cell migration in the developing nervous system, as well as axon guidance, dendrite development, and synapse formation. Given this wide range of roles, dysregulation of Wnt signaling could have any number of deleterious effects on neural development and thereby contribute in many different ways to the pathogenesis of neurodevelopmental disorders. Some major psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorders, are coming to be understood as subtle dysregulations of nervous system development, particularly of synapse formation and maintenance. This review will therefore touch on the importance of Wnt signaling to neurodevelopment generally, while focusing on accumulating evidence for a synaptic role of Wnt signaling. These observations will be discussed in the context of current understanding of the neurodevelopmental bases of major psychiatric diseases, spotlighting schizophrenia, bipolar disorder, and autism spectrum disorder. In short, this review will focus on the potential role of synapse formation and maintenance in major psychiatric disorders and summarize evidence that defective Wnt signaling could contribute to their pathogenesis via effects on these late neural differentiation processes

Role of multiple endocrine neoplasia type 1 mutational analysis in clinical practice.

OBJECTIVE: To review and assess the role of MEN1 mutational analysis in clinical practice. METHODS: Articles relevant to MEN1 mutation testing and screening were reviewed. RESULTS: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disorder characterized by the combined occurrence of tumors of the parathyroid glands, pancreatic islet cells, and anterior pituitary gland. MEN 1 is associated with premature mortality attributable primarily to malignant pancreatic neuroendocrine tumors and foregut carcinoids. The MEN1 gene is located on chromosome 11q13, and germline MEN1 mutations are highly penetrant and lead to tumor development in &gt;99% of patients by the age of 45 years. Current consensus guidelines recommend an integrated program of mutational analysis of the MEN1 gene and a combination of biochemical and radiologic screening to detect the early development of tumors and thereby reduce the morbidity and mortality associated with MEN 1. Our results reveal that MEN1 mutational analysis helps to confirm the clinical diagnosis, identify asymptomatic family members who have a MEN1 mutation and require screening from an early age, and identify the 50% of family members who do not have the MEN1 mutation and can therefore have the burden of screening and anxiety regarding potential disease removed. Moreover, MEN1 mutational analysis helps to resolve diagnostic challenges due to phenocopies, which occur in 5% to 10% of families with MEN 1. CONCLUSION: MEN1 mutational analysis facilitates clinical management and provides benefits to patients and families with MEN 1

Parafibromin--functional insights.

Parafibromin is a predominantly nuclear protein with a tumour suppressor role in the development of hereditary and nonhereditary parathyroid carcinomas, and the hyperparathyroidism-jaw tumour syndrome, which is associated with renal and uterine tumours. Parafibromin is a component of the highly conserved PAF1 complex, which regulates transcriptional events and histone modifications. The parafibromin/PAF1 complex regulates genes involved in cell growth and survival, and via these, parafibromin plays a pivotal role in embryonic development and survival of adults

Genetics of monogenic disorders of calcium and bone metabolism

Disorders of calcium homeostasis are the most frequent metabolic bone and mineral disease encountered by endocrinologists. These disorders usually manifest as primary hyperparathyroidism (PHPT) or hypoparathyroidism (HP), which have a monogenic aetiology in 5%-10% of cases, and may occur as an isolated endocrinopathy, or as part of a complex syndrome. The recognition and diagnosis of these disorders is important to facilitate the most appropriate management of the patient, with regard to both the calcium-related phenotype and any associated clinical features, and also to allow the identification of other family members who may be at risk of disease. Genetic testing forms an important tool in the investigation of PHPT and HP patients and is usually reserved for those deemed to be an increased risk of a monogenic disorder. However, identifying those suitable for testing requires a thorough clinical evaluation of the patient, as well as an understanding of the diversity of relevant phenotypes and their genetic basis. This review aims to provide an overview of the genetic basis of monogenic metabolic bone and mineral disorders, primarily focusing on those associated with abnormal calcium homeostasis, and aims to provide a practical guide to the implementation of genetic testing in the clinic