Prader-Willi syndrome (PWS), an imprinted neurodevelopmental disorder characterized by metabolic, sleep and neuropsychiatric features, is caused by the loss of paternal SNORD116, containing only non-coding RNAs (ncRNAs). The primary SNORD116 transcript is processed into small nucleolar RNAs (snoRNAs), which localize to nucleoli, and their spliced host gene 116HG, which is retained at its site of transcription. While functional complementation of the SNORD116 ncRNAs is a desirable goal for treating PWS, the mechanistic requirements of SNORD116 RNA processing are poorly understood. Here we developed and tested a novel transgenic mouse which ubiquitously expresses Snord116 on both a wild-type and a Snord116 paternal deletion (Snord116+/-) background. Interestingly, while the Snord116 transgene was ubiquitously expressed in multiple tissues, splicing of the transgene and production of snoRNAs was limited to brain tissues. Knockdown of Rbfox3, encoding neuron-specific splicing factor neuronal nuclei (NeuN) in Snord116+/--derived neurons, reduced splicing of the transgene in neurons. RNA fluorescence in situ hybridization for 116HG revealed a single significantly larger signal in transgenic mice, demonstrating colocalization of transgenic and endogenous 116HG RNAs. Similarly, significantly increased snoRNA levels were detected in transgenic neuronal nucleoli, indicating that transgenic Snord116 snoRNAs were effectively processed and localized. In contrast, neither transgenic 116HG nor snoRNAs were detectable in either non-neuronal tissues or Snord116+/- neurons. Together, these results demonstrate that exogenous expression and neuron-specific splicing of the Snord116 locus are insufficient to rescue the genetic deficiency of Snord116 paternal deletion. Elucidating the mechanisms regulating Snord116 processing and localization is essential to develop effective gene replacement therapies for PWS.

Cancer is a disease that continues to plague our modern society. Among all types of cancer, breast cancer is now the most common type of cancer occurring in women worldwide. Various factors, including genetics, lifestyle, and the environment, have contributed to the rise in the prevalence of breast cancer among women of all socioeconomic strata. Therefore, proper screening for early diagnosis and treatment becomes a major factor when fighting the disease. Artificial intelligence (AI) continues to revolutionize various spheres of our lives with its numerous applications. Using AI in the existing screening process makes obtaining results even easier and more convenient. Faster, more accurate results are some of the benefits of AI methods in breast cancer screening. Nonetheless, there are many challenges in the process of the integration of AI that needs to be addressed systematically. The following is a review of the application of AI in breast cancer screening.

Prader-Willi syndrome (PWS), an imprinted neurodevelopmental disorder characterized by metabolic, sleep, and neuropsychiatric features, is caused by the loss of paternal SNORD116, containing only noncoding RNAs. The primary SNORD116 transcript is processed into small nucleolar RNAs (snoRNAs), which localize to nucleoli, and their spliced host gene 116HG, which is retained at its site of transcription. While functional complementation of the SNORD116 noncoding RNAs is a desirable goal for treating PWS, the mechanistic requirements of SNORD116 RNA processing are poorly understood. Here we developed and tested a novel transgenic mouse which ubiquitously expresses Snord116 on both a wild-type and Snord116 paternal deletion (Snord116 +/-) background. Interestingly, while the Snord116 transgene was ubiquitously expressed in multiple tissues, splicing of the transgene and production of snoRNAs was limited to brain tissues. Knockdown of Rbfox3, encoding neuron-specific splicing factor NeuN, in Snord116 +/--derived neurons reduced splicing of the transgene in neurons. RNA fluorescent in situ hybridization for 116HG revealed a single significantly larger signal in transgenic mice, demonstrating colocalization of transgenic and endogenous 116HG RNAs. Similarly, significantly increased snoRNA levels were detected in transgenic neuronal nucleoli, indicating that transgenic Snord116 snoRNAs were effectively processed and localized. In contrast, neither transgenic 116HG nor snoRNAs were detectable in either non-neuronal tissues or Snord116 +/neurons. Together, these results demonstrate that exogenous expression and neuron-specific splicing of the Snord116 locus are insufficient to rescue the genetic deficiency of Snord116 paternal deletion. Elucidating the mechanisms regulating Snord116 processing and localization are essential to develop effective gene replacement therapies for PWS.