Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with loss of nuclear transactive response DNA-binding protein 43 (TDP-43). Here we identify that TDP-43 regulates expression of the neuronal growth-associated factor stathmin-2. Lowered TDP-43 levels, which reduce its binding to sites within the first intron of stathmin-2 pre-messenger RNA, uncover a cryptic polyadenylation site whose utilization produces a truncated, non-functional mRNA. Reduced stathmin-2 expression is found in neurons trans-differentiated from patient fibroblasts expressing an ALS-causing TDP-43 mutation, in motor cortex and spinal motor neurons from patients with sporadic ALS and familial ALS with GGGGCC repeat expansion in the C9orf72 gene, and in induced pluripotent stem cell (iPSC)-derived motor neurons depleted of TDP-43. Remarkably, while reduction in TDP-43 is shown to inhibit axonal regeneration of iPSC-derived motor neurons, rescue of stathmin-2 expression restores axonal regenerative capacity. Thus, premature polyadenylation-mediated reduction in stathmin-2 is a hallmark of ALS-FTD that functionally links reduced nuclear TDP-43 function to enhanced neuronal vulnerability

Female Electoral Success in State Legislative Races: A Case Study Review of Gender Influence on Incumbency, Fundraising, Recruitment, and Policy

Since the beginning of recorded history, female representation in elective office has been drastically lower than that of the U.S. population. Over the years, there have been many records set for women in office, including the 28% of the 118th Congress represented by women. Considering both chambers of Congress, the House and the Senate, women account for 153 of the 540 seats of the body. This number marks a record high, demonstrating commitment and strength in numbers by women in politics. While 28% female is still a small number in comparison to the amount of women accounted for in the United States population, this jump in percentage reflects a 59% increase in the number of women in office from the I 12th Congress one decade ago (Leppert and Desilver, 2023). It is no secret that the female population is more heavily represented in state legislatures; however, they only occupy 30.5% of state legislative seats in the United States (CA WP, 2022). This is not just a nationwide phenomenon, as women across the globe have worked hard to break glass ceilings and claim their seat at the table in the political arena. One may ask themselves what the world would look like if we had elected more women since the beginning of our nation\u27s founding. This thought challenges us to consider what our laws, policies, and governmental structure may have become if we had more equal representation. Although we do not have all of these answers, there is work to be done to better understand how our nation can achieve a more representative democracy. To fully understand the development of a woman\u27s role in politics, it is often best to understand where it all began. For years, Elizabeth Cady Stanton, a women\u27s rights leader, was tired of watching women be denied a seat at the table. In 1866, Stanton stood firm alongside her mission and is recognized as the first woman to run for the United State House of Representatives, despite her grueling loss for the New York seat. Her courage started a movement, and six years later Victoria Woodhull ran for President of the United States. As you can infer, Woodhull was unsuccessful in her attempt, but her courage once again spoke volumes for the female community. In 1884. Belva Lockwood was the first woman admitted to the practice of law. Because of the dedication and bravery of these women and many others, women like me are able to research and write about their stories. While all of these stories are incredibly important, pioneering the way for women today, we still have a good bit of work to do. This past March, I met with State Senator Karen Lewi\u27s Young. She told me that she was the first woman elected to represent her region of Maryland, and she was incredibly proud of this feat. In the middle of our conversation, she looked at me and said, Young lady, it\u27s about time that women reach equal representation, and I am proud to be a part of it.\u27\u27 I was immediately inspired and reminded of the brevity of this topic. As mentioned before, there are historically more women serving in state level legislatures than other levels of public service. I have always believed that change often starts small, in this case locally, and causes a ripple effect. Due to this fact, my study focuses on women making a bid for state-level office, and seeks to understand the factors that help them win their seat. When speaking in terms of an election, there are several factors that play a part. We can analyze these factors to create a more holistic look at female electoral success, and achieve our goal of becoming closer to pinpointing the most influential factor in getting women elected. After a job with a local mayor in Northeast Arkansas, I knew then that I wanted to dedicate a piece of my career to public service. Throughout my study, I intend to focus on female electoral success with emphasis on the incumbency advantage, fundraising efforts, recruitment methods, partisan effect, and policy influence

The Effect of Protein and Omega-3 Fatty Acid Supplementation on Regulation of Sleep and Mood in Postmenopausal Women

The older population of the United States is in a period of rapid growth [1]. population of those in the United States aged 65 or older will double to about 72 million in the next 25 year [1]. This population is at increased risk for obesity, chronic diseases, decreased quality of life, and premature death. Therefore, guidelines for healthy aging are desperately needed. In 2015 alone, 67.7% of adults in the United States aged 65 or older reported having two or more chronic conditions [2]. Treatment for those in the older population afflicted by multiple chronic conditions alone accounts for 66% of the United States’ total health care budget [1]. In 2018, for the third year in a row, Arkansas was one of nine states with an adult obesity rate at or above 35 percent [3]. The obesity prevalence in Arkansans 65 years of age and older was reported to be 30.1% for 2018 and is projected to continue with an increasingly upward trajectory. In the United States, Arkansas was identified as having the 4th highest-ranked state with regard to overweight and obesity percentiles for adults. Arkansas was also identified as the 4th highest-ranked state for number of adults diagnosed with type 2 diabetes mellitus (T2DM). Additionally, in Arkansas alone 23.4% of adults aged 65 years of age or older were currently diagnosed with T2DM in 2015, with an expected increase in this percentage [2]. Poor sleep has been identified as one potential cause for this dramatic decline in health [4]. Sleep disorders are highly prevalent in older adults with 50% or more older adults being currently diagnosed with a clinical sleeping disorder [5]. A lack of sleep schedule regularity in addition to poor sleep quality puts older adults at significantly higher risk for cognitive and functional decline [5]. Sleep loss in older adults has been specifically linked to an increased risk of T2DM and obesity [4]. While aging is linked to a general 5 decline in total sleep time and sleep efficiency, sleep efficiency has been shown to significantly decrease past age 60 [6]. Adequate nutrition has the potential to combat dysregulated sleep and mood

Love Conquers Death: Mythological Subversion and Emotional Triumph in “The Tale of Beren and Luthien”

Though The Hobbit and The Lord of the Rings sit at the forefront of J.R.R. Tokien’s expansive legendarium, there is one work that sits at the center of his expansive world. Published as chapter 19 of The Silmarillion, Of Beren and Luthien, also referred to as The Tale of Beren and Luthien is the beating heart of Tolkien’s mythology. It is perhaps his most important work, consistently developed over the course of his life. It is a true mythological epic, a story of good and evil, monsters and heroes, great treasure and constant peril. More than anything it is a powerful and moving tale of love, a showcase of its power, and a written testament to Tolkien’s own love. Of Beren and Luthien subverts traditional mythological expectations, and acts as a powerful thread that stretches beyond The Silmarillion, into The Appendices of The Lord of the Rings and Tolkien\u27s life itself

Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.

Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Transcriptome-pathology correlation identified casein kinase 1ε (CSNK1E) mRNA as tightly correlated to levels of pTDP-43 in sALS patients. Enhanced crosslinking and immunoprecipitation in human sALS patient- and healthy control-derived frontal cortex, revealed that TDP-43 binds directly to and regulates the expression of CSNK1E mRNA. Additionally, we were able to show that pTDP-43 itself binds RNA. CK1E, the protein product of CSNK1E, in turn interacts with TDP-43 and promotes cytoplasmic accumulation of pTDP-43 in human stem-cell-derived MNs. Pathological TDP-43 phosphorylation is therefore, reciprocally regulated by CK1E activity and TDP-43 RNA binding. Our framework of transcriptome-pathology correlations identifies candidate genes with relevance to novel mechanisms of neurodegeneration

Cochlear Implant Training Model

Currently available training methods for cochlear implant surgeries such as cadavers and imaging systems are expensive and available for a limited number of training sessions. With the goal of decreasing risk factors associated with cochlear implant surgery, our team developed a cochlear implant training model prototype that is designed to provide a trial-and-error, tactile training method for developing force perception levels required to avoid causing damage to the cochlea. This model is designed to utilize a disposable material that ruptures when exposed to critical force levels. A material testing device was developed and utilized to test an assortment of easily accessible, thin materials that could be used by the training model. Further testing is still required before selecting the final material for the training model. An overview of potential material selection methods is given to improve future material testing results

Interpersonal and Shared Decision Making models of communication applied to simulated requests for organ donation

Using an analogue format, the present study evaluated the viability of relationship and interactional concepts that have been applied to the physician-patient interaction to the field of organ donation by examining the donation request process between procurement coordinators and simulated families. Interpersonal processes were assessed using behavioral ratings by independent observers. Procurement coordinators were viewed as being more submissive than dominant and more friendly than hostile. Family members were viewed as being more hostile than friendly, more dominant and hostile than submissive or friendly, disclosing slightly more personal information than medical information, and engaging in slightly more shared decision making than providing medical information. Procurement coordinator gender and ethnicity and family ethnicity influenced interpersonal behavior. Several interpersonal variables were associated with measures of the “decision to donate” obtained from raters and simulated families. Implications for the field of organ donation and the training of procurement coordinators are discussed

Brand origin identification by consumers: A classification perspective

The authors apply a classification perspective to (1) examine the extent to which consumers can identify the correct country of origin (COO) of different brands of consumer durables, (2) investigate the factors facilitating/hindering correct COO identification, and (3) trace the implications of correct/incorrect COO identification on brand evaluation. The results from a U.K. sample indicate that consumers' ability to classify brands correctly according to their origin is limited and also reveal substantial differences in the classification of different brands to their COO. Moreover, the key antecedent of correct COO identification is consumer ethnocentrism, with sociodemographics (e.g., age, gender) also playing a role. Finally, the authors find that though there are differences in brand evaluations depending on whether the correct COO was identified, such differences are not observed for all brands investigated