The Inhibition of Splicing of Glucose-6-phosphate Dehydrogenase mRNA During Starvation by Heterogeneous Nuclear Ribonucleoprotein K

Splicing of nascent RNA transcripts is an essential step in gene expression and a target of nutrient regulation. Glucose-6-phosphate dehydrogenase (G6PD) is a lipogenic gene whose expression is regulated exclusively at this posttranscriptional stage. Expression of G6PD mRNA increases 15- to 17-fold during refeeding and is inhibited 80-90% by starvation and the addition of polyunsaturated fat to the diet. The large changes in the accumulation of G6PD mRNA are due to changes the rate of pre-mRNA splicing and not changes in its transcription. In this regard, dietary carbohydrate enhances intron removal, which increases the accumulation of G6PD mRNA. Starvation alters pre-mRNA splicing by decreasing the rate of intron removal, leading to intron retention and a decrease in the accumulation of mature mRNA. A regulatory element within exon 12 of the G6PD pre-mRNA that contains both an ESS and an ESE mediates these changes in splicing efficiency. SR proteins, like SRp20, along with hnRNP K, L and A2/B1 bind to this regulatory region. Starvation caused an increase in the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) K protein and this increase coincided with the increase in the binding of hnRNP K to the regulatory element and a decrease in the expression of G6PD mRNA in vivo. HnRNP K bound to two C-rich motifs forming an ESS within exon 12. Overexpression of hnRNP K decreased the splicing and expression of G6PD mRNA, while siRNA-mediated depletion of hnRNP K caused an increase in the splicing and expression of G6PD mRNA. HnRNP K binding to the C- rich motifs blocked binding of serine-arginine rich, splicing factor 3 (SRSF3), a splicing enhancer. Thus hnRNP K is a nutrient regulated splicing factor responsible for the inhibition of the splicing of G6PD during starvation

The Most Common Vocal Fault in the Baritone Voice

The purpose of this research project is to create an approachable guide to avoiding the most common vocal fault found in the baritone singing voice. The specific fault being discussed has been coined the “baritone swallow.” This document will explore the history of the baritone singing voice along with information regarding vocal fach identification, an in-depth study of this common vocal fault frequently experienced by baritone singers, and a fault-specific guide to identifying and addressing the “baritone swallow.

A Human Being Wrote This Law Review Article: GPT-3 and the Practice of Law

Artificial intelligence tools can now “write” in such a sophisticated manner that they fool people into believing that a human wrote the text. None are better at writing than GPT-3, released in 2020 for beta testing and coming to commercial markets in 2021. GPT-3 was trained on a massive dataset that included scrapes of language from sources ranging from the NYTimes to Reddit boards. And so, it comes as no surprise that researchers have already documented incidences of bias where GPT-3 spews toxic language. But because GPT-3 is so good at “writing,” and can be easily trained to write in a specific voice — from classic Shakespeare to Taylor Swift — it is poised for wide adoption in the field of law. This Article explores the ethical considerations that will follow from GPT-3’s introduction into lawyers’ practices. GPT-3 is new, but the use of AI in the field of law is not. AI has already thoroughly suffused the practice of law. GPT-3 is likely to take hold as well, generating some early excitement that it and other AI tools could help close the access to justice gap. That excitement should nevertheless be tempered with a realistic assessment of GPT-3’s tendency to produce biased outputs. As amended, the Model Rules of Professional Conduct acknowledge the impact of technology on the profession and provide some guard rails for its use by lawyers. This Article is the first to apply the current guidance to GPT-3, concluding that it is inadequate. I examine three specific Model Rules — Rule 1.1 (Competence), Rule 5.3 (Supervision of Nonlawyer Assistance), and Rule 8.4(g) (Bias) — and propose amendments that focus lawyers on their duties and require them to regularly educate themselves about pros and cons of using AI to ensure the ethical use of this emerging technology

Guides to administrator behavior

Rules of thumb for everyday life as an administrator

Blockchain Safe Harbor? Applying the Lessons Learned From Early Internet Regulation

It has been more than a quarter century since Congress enacted twin safe harbor provisions to help protect and encourage the growth of a nascent internet by removing some liability and regulatory uncertainty. Today, there are calls for a similar safe harbor provision for blockchain, the technology behind cryptocurrencies and smart contracts. What lessons have we learned from the implementation of the internet safe harbor provisions, Section 230 of the Communications Decency Act, and Section 512 of the Digital Millennium Copyright Act? This Article charts the history of those provisions and their judicial construction over the decades. It also examines the criticism of these safe harbors, including that they have done too much to immunize large technology companies from the harm caused by their products. Blockchain technology shares a common history with the internet, and blockchain today is in a similar position to internet in the mid 1990s. Through cataloguing the lessons of internet regulation, this Article provides important considerations for regulators to bear in mind as they consider implementing safe harbor provisions for blockchain applications