Stem cell models of Angelman syndrome.

Angelman syndrome (AS) is an imprinted neurodevelopmental disorder that lacks a cure, characterized by developmental delay, intellectual impairment, seizures, ataxia, and paroxysmal laughter. The condition arises due to the loss of the maternally inherited copy of the UBE3A gene in neurons. The paternally inherited UBE3A allele is unable to compensate because it is silenced by the expression of an antisense transcript (UBE3A-ATS) on the paternal chromosome. UBE3A, encoding enigmatic E3 ubiquitin ligase variants, regulates target proteins by either modifying their properties/functions or leading them to degradation through the proteasome. Over time, animal models, particularly the Ube3a mat-/pat+ Knock-Out (KO) mice, have significantly contributed to our understanding of the molecular mechanisms underlying AS. However, a shift toward human pluripotent stem cell models (PSCs), such as human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), has gained momentum. These stem cell models accurately capture human genetic and cellular characteristics, offering an alternative or a complement to animal experimentation. Human stem cells possess the remarkable ability to recapitulate neurogenesis and generate "brain-in-a-dish" models, making them valuable tools for studying neurodevelopmental disorders like AS. In this review, we provide an overview of the current state-of-the-art human stem cell models of AS and explore their potential to become the preclinical models of choice for drug screening and development, thus propelling AS therapeutic advancements and improving the lives of affected individuals.

Non-coding antisense transcripts: fine regulation of gene expression in cancer.

Natural antisense transcripts (NATs) are coding or non-coding RNA sequences transcribed on the opposite direction from the same genomic locus. NATs are widely distributed throughout the human genome and seem to play crucial roles in physiological and pathological processes, through newly described and targeted mechanisms. NATs represent the intricate complexity of the genome organization and constitute another layer of potential targets in disease. Here, we focus on the interesting and unique role of non-coding NATs in cancer, paying particular attention to those acting as miRNA sponges.

[Breast cancer at Pico Island (1998-2008): an epidemiological perspective]. / Cancro da mama na ilha do pico (1998-2008): uma perspectiva epidemiológica.

INTRODUCTION: Neoplasic disease has been assuming an increasingly relevant role in the world's public health. Breast cancer is the most common cancer and the second cause of death by neoplasia in women. In the Portuguese population, breast cancer is the main cause of death by neoplasia in females. Among the Azorean women, the most frequently diagnosed malignant tumor is breast cancer, Pico Island being the third in terms of cancer incidence in the region. The risk factors are well known, well established and some of them can be prevented. Despite the great incidence of breast cancer, in the general population, particularly among the youngest, the knowledge about the disease is quite limited. The aims of this study are to characterize and identify the risk factors of women with breast cancer diagnose between 1998 and 2008 residing in Pico's island and, simultaneously to evaluate the knowledge of the students in Pico island about this disease. METHODS AND POPULATION: The method used for the gathering of the data in both cases was an anonymous and confidential questionnaire. In study 1 the questionnaire was conducted by an interviewer after the women's consent. Study 2 was performed in the three secondary schools of Pico island. RESULTS: The incidence rate of breast cancer in Pico island women is higher than the national incidence rate. There was an enormous variability in the incidence rates calculated for each year, with no clear tendency. The main responsible for the appearance of breast cancer in this population could be a conjugation of factors and not only a single isolated factor. The risk factors that stand out are: sedentariness (71.4%), family history (47.6%) and obesity (44.4%). The 295 students interviewed aged between 15 and 21 years. Of the total, 43 had relatives with breast cancer, however the majority (56.3%) assumes to be little informed about this disease. CONCLUSIONS: Through study 1 we conclude that there is a combination of hereditary and environmental risk factors, modifiable and non modifiable risk factors that may contribute to the onset of breast cancer. It is important to encourage changes in the life style of the women and rising of awareness towards risk factors. For the study of the student population, we conclude that the students have a very limited degree of knowledge of the disease; however, they assumed the will to more information, which leaves an open door for future formation and awareness actions.